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@article{
 title = {A Brazilian Rare-Disease Center’s Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF},
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 abstract = {Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid β-glucocerebrosidase (Gcase). Three clinical forms of Gaucher’s disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol–acetonitrile–water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = −0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1–157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.},
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 author = {Vernet Machado Bressan Wilke, Matheus and Iop, Gabrielle Dineck and Faqueti, Larissa and Lemos da Silva, Layzon Antonio and Kubaski, Francyne and Poswar, Fabiano O. and Michelin-Tirelli, Kristiane and Randon, Dévora and Borelli, Wyllians Vendramini and Giugliani, Roberto and Schwartz, Ida Vanessa D.},
 doi = {10.3390/ijms25052870},
 journal = {International Journal of Molecular Sciences},
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Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid β-glucocerebrosidase (Gcase). Three clinical forms of Gaucher’s disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol–acetonitrile–water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = −0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1–157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.

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 created = {2023-06-11T20:57:21.616Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-06-11T20:57:21.616Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {inbook},
 author = {Giugliani, Roberto and de Oliveira Poswar, Fabiano and Kubaski, Francyne},
 doi = {10.1007/978-3-319-66816-1_1337-1},
 chapter = {Mucopolysaccharidoses I-IX and MPSPS},
 title = {Genetic Syndromes}
}

@article{
 title = {Generative artificial intelligence as a tool for learning genetic syndrome facial gestalt},
 type = {article},
 year = {2023},
 pages = {122},
 id = {597c71b4-51c7-3c8a-9ca2-61ea5db1b3cc},
 created = {2023-10-19T15:14:38.631Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-10-19T15:14:42.525Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Poswar, F.O.},
 doi = {10.5281/zenodo.10015994},
 journal = {Anais do XXXIV Congresso Brasileiro de Genética Médica}
}

@article{
 title = {Consecutive Liver and Bone Marrow Transplantation for Erythropoietic Protoporphyria: Case Report and Literature Review},
 type = {article},
 year = {2023},
 pages = {416-422},
 volume = {45},
 websites = {https://journals.lww.com/10.1097/MPH.0000000000002738},
 month = {10},
 id = {f87f4238-3b0c-3294-9d43-e6c09a4e1136},
 created = {2023-10-19T15:14:38.641Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-10-19T15:14:38.641Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Portich, Júlia Plentz and Ribeiro, Aline Sinhorelo and Rodrigues Taniguchi, Adriano Nori and Backes, Ariane and de Souza, Carolina Fischinger Moura and Kieling, Carlos Oscar and Scherer, Fernanda Fetter and de Oliveira Poswar, Fabiano and Leipnitz, Ian and Doederlein Schwartz, Ida Vanessa and Sekine, Leo and Rigoni, Lisandra Della Costa and Marquardt da Silveira, Luciana and de Almeida Furlanetto, Marina and Adami, Marina Rossato and Breunig, Raquel Cristine and Guedes, Renata Rostirola and do Amaral, Sheila Nogueira and Gonçalves Vieira, Sandra Maria and de Brum Soares, Tahiane and Silva, Thiago Oliveira and da Rocha Silla, Lúcia Mariano and Astigarraga, Claudia Caceres and Paz, Alessandra Aparecida and Daudt, Liane Esteves},
 doi = {10.1097/MPH.0000000000002738},
 journal = {Journal of Pediatric Hematology/Oncology},
 number = {7}
}

@article{
 title = {Oral Dantrolene Reduces Myalgia and Hyperckemia in a Child with RYR1-Related Exertional Myalgia/Rhabdomyolysis},
 type = {article},
 year = {2023},
 pages = {1-5},
 websites = {https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JND-230007},
 month = {9},
 day = {28},
 id = {2e9754b8-5bcb-3247-b8b4-d75877894e35},
 created = {2023-10-19T15:14:38.952Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-10-19T15:14:38.952Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {RYR1-related exertional myalgia/rhabdomyolysis (ERM) is an underrecognized condition, which can cause limiting muscle symptoms, and may account for more than one-third of undiagnosed rhabdomyolysis cases. Dantrolene has shown promising results in controlling muscle symptoms in individuals with ERM, however, its use in children remains poorly documented. This case report presents the successful treatment of a 5-year-old patient with ERM using oral dantrolene. The patient experienced notable improvements, including a reduction in the frequency and intensity of myalgia episodes, no hospitalizations due to rhabdomyolysis, a substantial decrease in creatine phosphokinase (CPK) levels, and enhanced performance on the 6-minute walk test. The use of dantrolene was well-tolerated, and no significant adverse effects were observed. This report adds to the existing evidence supporting the effectiveness of oral dantrolene in managing ERM, and, to the best of our knowledge, this is the first report of the use of dantrolene in a pediatric patient for controlling anesthesia-independent muscle symptoms.},
 bibtype = {article},
 author = {de Lima Silva, Elis Vanessa and Donis, Karina Carvalho and Machado, Fabiana Rita Camara and Medeiros, Leonardo Simão and Aschoff, Carlos Alberto de Moura and de Souza, Carolina Fischinger Moura and Poswar, Fabiano de Oliveira and Saute, Jonas Alex Morales},
 doi = {10.3233/JND-230007},
 journal = {Journal of Neuromuscular Diseases}
}

RYR1-related exertional myalgia/rhabdomyolysis (ERM) is an underrecognized condition, which can cause limiting muscle symptoms, and may account for more than one-third of undiagnosed rhabdomyolysis cases. Dantrolene has shown promising results in controlling muscle symptoms in individuals with ERM, however, its use in children remains poorly documented. This case report presents the successful treatment of a 5-year-old patient with ERM using oral dantrolene. The patient experienced notable improvements, including a reduction in the frequency and intensity of myalgia episodes, no hospitalizations due to rhabdomyolysis, a substantial decrease in creatine phosphokinase (CPK) levels, and enhanced performance on the 6-minute walk test. The use of dantrolene was well-tolerated, and no significant adverse effects were observed. This report adds to the existing evidence supporting the effectiveness of oral dantrolene in managing ERM, and, to the best of our knowledge, this is the first report of the use of dantrolene in a pediatric patient for controlling anesthesia-independent muscle symptoms.

@article{
 title = {Progression of Cardiovascular Manifestations in Adults and Children With Mucopolysaccharidoses With and Without Enzyme Replacement Therapy},
 type = {article},
 year = {2022},
 volume = {8},
 websites = {https://www.frontiersin.org/articles/10.3389/fcvm.2021.801147/full},
 month = {1},
 day = {12},
 id = {005df6ca-33df-39f8-8db0-0f7fa76e028e},
 created = {2022-04-27T14:43:03.280Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2022-04-27T14:43:03.280Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Cardiovascular involvement is among the main features of MPS disorders and it is also a significant cause of morbidity and mortality. The range of manifestations includes cardiac valve disease, conduction abnormalities, left ventricular hypertrophy, and coronary artery disease. Here, we assessed the cardiovascular manifestations in a cohort of children and adults with MPS I, II, IV, and VI, as well as the impact of enzyme replacement therapy (ERT) on those manifestations.},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Santos, Hallana Souza and Santos, Angela Barreto Santiago and Berger, Solano Vinicius and Souza, Carolina Fischinger Moura de and Giugliani, Roberto and Baldo, Guilherme},
 doi = {10.3389/fcvm.2021.801147},
 journal = {Frontiers in Cardiovascular Medicine}
}

Background: Cardiovascular involvement is among the main features of MPS disorders and it is also a significant cause of morbidity and mortality. The range of manifestations includes cardiac valve disease, conduction abnormalities, left ventricular hypertrophy, and coronary artery disease. Here, we assessed the cardiovascular manifestations in a cohort of children and adults with MPS I, II, IV, and VI, as well as the impact of enzyme replacement therapy (ERT) on those manifestations.

@article{
 title = {Overlapping Etiologies in a Young Patient with Severe Myocarditis: A Case Report},
 type = {article},
 year = {2022},
 pages = {116-119},
 volume = {2},
 websites = {https://www.abcheartfailure.org/article/overlapping-etiologies-in-a-young-patient-with-severe-myocarditis-a-case-report/},
 month = {4},
 day = {12},
 id = {b9d3e45a-d65c-3b1e-b09a-467689cd1bcb},
 created = {2022-05-05T14:09:27.738Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2022-05-05T14:09:27.738Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Oliveira, Thaís Martins de and Scolari, Fernando Luis and Poswar, Fabiano de Oliveira and Oliveira, Francine Hehn de and Stein, Ricardo and Goldraich, Lívia Adams},
 doi = {10.36660/abchf.20220022},
 journal = {ABC Heart Fail Cardiomyop},
 number = {1}
}

@article{
 title = {Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome},
 type = {article},
 year = {2022},
 pages = {annrheumdis-2022-222629},
 websites = {https://doi.org/10.1136/annrheumdis-2022-222629,https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2022-222629},
 month = {7},
 day = {22},
 id = {11d9c0f2-46b6-3f10-8041-2876393faca3},
 created = {2022-07-28T13:23:13.916Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2022-12-11T18:14:08.720Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Kozycki, Christina Torres and Kodati, Shilpa and Huryn, Laryssa and Wang, Hongying and Warner, Blake M and Jani, Priyam and Hammoud, Dima and Abu-Asab, Mones S and Jittayasothorn, Yingyos and Mattapallil, Mary J and Tsai, Wanxia Li and Ullah, Ehsan and Zhou, Ping and Tian, Xiaoying and Soldatos, Ariane and Moutsopoulos, Niki and Kao-Hsieh, Marie and Heller, Theo and Cowen, Edward W and Lee, Chyi-Chia Richard and Toro, Camilo and Kalsi, Shelley and Khavandgar, Zohreh and Baer, Alan and Beach, Margaret and Long Priel, Debra and Nehrebecky, Michele and Rosenzweig, Sofia and Romeo, Tina and Deuitch, Natalie and Brenchley, Laurie and Pelayo, Eileen and Zein, Wadih and Sen, Nida and Yang, Alexander H and Farley, Gary and Sweetser, David A and Briere, Lauren and Yang, Janine and de Oliveira Poswar, Fabiano and Schwartz, Ida and Silva Alves, Tamires and Dusser, Perrine and Koné-Paut, Isabelle and Touitou, Isabelle and Titah, Salah Mohamed and van Hagen, Petrus Martin and van Wijck, Rogier T A and van der Spek, Peter J and Yano, Hiromi and Benneche, Andreas and Apalset, Ellen M and Jansson, Ragnhild Wivestad and Caspi, Rachel R and Kuhns, Douglas Byron and Gadina, Massimo and Takada, Hidetoshi and Ida, Hiroaki and Nishikomori, Ryuta and Verrecchia, Elena and Sangiorgi, Eugenio and Manna, Raffaele and Brooks, Brian P and Sobrin, Lucia and Hufnagel, Robert and Beck, David and Shao, Feng and Ombrello, Amanda K and Aksentijevich, Ivona and Kastner, Daniel L},
 doi = {10.1136/annrheumdis-2022-222629},
 journal = {Annals of the Rheumatic Diseases}
}

@article{
 title = {Convergent molecular mechanisms underlying cognitive impairment in mucopolysaccharidosis type II},
 type = {article},
 year = {2022},
 pages = {2089-2102},
 volume = {37},
 websites = {https://link.springer.com/10.1007/s11011-021-00872-8},
 month = {8},
 day = {19},
 id = {667d20e8-06ae-3dc0-b867-5c4ce06b39ca},
 created = {2022-12-11T19:01:02.851Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2022-12-22T19:53:39.024Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Corrêa, Thiago and Poswar, Fabiano and Santos-Rebouças, Cíntia B.},
 doi = {10.1007/s11011-021-00872-8},
 journal = {Metabolic Brain Disease},
 number = {6}
}

@article{
 title = {Diagnosis and Emerging Treatment Strategies for Mucopolysaccharidosis VII (Sly Syndrome)},
 type = {article},
 year = {2022},
 pages = {1143-1155},
 volume = {Volume 18},
 month = {12},
 id = {d39f9765-a45d-34d4-a9d4-8957329bfac6},
 created = {2022-12-22T17:35:38.870Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2022-12-22T20:09:15.573Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Henriques Nehm, Johanna and Kubaski, Francyne and Poletto, Edina and Giugliani, Roberto},
 doi = {10.2147/TCRM.S351300},
 journal = {Therapeutics and Clinical Risk Management}
}

@inproceedings{
 title = {Capillary hyperglycemia in infants-A manifestation of endocrinological urgency, or not},
 type = {inproceedings},
 year = {2022},
 pages = {334},
 volume = {95},
 issue = {SUPPL 2},
 publisher = {KARGER ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND},
 id = {05d596ba-3d95-3f39-8eb5-dfaba7e0073d},
 created = {2023-06-12T09:16:39.223Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-06-12T09:16:39.223Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 source_type = {CONF},
 private_publication = {false},
 bibtype = {inproceedings},
 author = {Galan, Camila de Assis and Scheidt, Maria Isabel and Pedroso de Paula, Leila Cristina and de Lima Silva, Elis Vanessa and Medeiros, Leonardo Simao and Poswar, Fabiano de Oliveira},
 booktitle = {HORMONE RESEARCH IN PAEDIATRICS}
}

@article{
 title = {Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series},
 type = {article},
 year = {2021},
 keywords = {AHDS,Allan-Herndon-Dudley syndrome,MCT8,MCT8 deficiency,monocarboxylate transporter 8,thyroid hormone transport},
 pages = {539-553},
 volume = {106},
 id = {49573ce4-772a-39a3-a5ab-aeaa8e03fb4a},
 created = {2021-01-16T15:30:17.693Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:31:40.699Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {CONTEXT: Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes. METHODS: We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts. RESULTS: Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patient-derived fibroblasts, challenging a causal relationship. Two brothers with classical MCT8 deficiency had a truncating c.1695delT;p.(Val566*) variant that completely inactivated MCT8 in vitro. The 3 other boys had relatively less-severe clinical features and harbored frameshift variants that elongate the MCT8 protein [c.1805delT;p.(Leu602HisfsTer680) and c.del1826-1835;p.(Pro609GlnfsTer676)] and retained ~50% residual activity. Additional truncating variants within transmembrane domain 12 were fully inactivating, whereas those within the intracellular C-terminal tail were tolerated. CONCLUSIONS: Variants affecting the intracellular C-terminal tail of MCT8 are likely benign unless they cause frameshifts that elongate the MCT8 protein. These findings provide clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8.},
 bibtype = {article},
 author = {van Geest, Ferdy S. and Meima, Marcel E. and Stuurman, Kyra E. and Wolf, Nicole I. and van der Knaap, Marjo S. and Lorea, Cláudia F. and Poswar, Fabiano O. and Vairo, Filippo and Brunetti-Pierri, Nicola and Cappuccio, Gerarda and Bakhtiani, Priyanka and de Munnik, Sonja A. and Peeters, Robin P. and Visser, W. Edward and Groeneweg, Stefan},
 doi = {10.1210/clinem/dgaa795},
 journal = {The Journal of clinical endocrinology and metabolism},
 number = {2}
}

CONTEXT: Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes. METHODS: We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts. RESULTS: Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patient-derived fibroblasts, challenging a causal relationship. Two brothers with classical MCT8 deficiency had a truncating c.1695delT;p.(Val566*) variant that completely inactivated MCT8 in vitro. The 3 other boys had relatively less-severe clinical features and harbored frameshift variants that elongate the MCT8 protein [c.1805delT;p.(Leu602HisfsTer680) and c.del1826-1835;p.(Pro609GlnfsTer676)] and retained ~50% residual activity. Additional truncating variants within transmembrane domain 12 were fully inactivating, whereas those within the intracellular C-terminal tail were tolerated. CONCLUSIONS: Variants affecting the intracellular C-terminal tail of MCT8 are likely benign unless they cause frameshifts that elongate the MCT8 protein. These findings provide clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8.

@article{
 title = {Impact of COVID-19 on treatment and follow-up in patients with selected lysosomal diseases in a Brazilian center},
 type = {article},
 year = {2021},
 pages = {S98},
 volume = {132},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719220305059},
 month = {2},
 id = {4e7d6554-7ca2-32a4-a1b7-f0c5cba187e6},
 created = {2021-03-31T01:31:17.955Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-03-31T01:31:17.955Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Schwartz, Ida V.D. and Silva, Thiago O. and Poswar, Fabiano O. and Souza, Carolina F.M. and Giugliani, Roberto},
 doi = {10.1016/j.ymgme.2020.12.237},
 journal = {Molecular Genetics and Metabolism},
 number = {2}
}

@inbook{
 type = {inbook},
 year = {2021},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1877117321000429},
 id = {34e2494a-688b-3109-8f92-2ca9dd6c6067},
 created = {2021-07-04T13:54:26.305Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-07-04T13:54:26.305Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {inbook},
 author = {Pimentel-Vera, Luisa Natalia and Poletto, Edina and Gonzalez, Esteban Alberto and de Oliveira Poswar, Fabiano and Giugliani, Roberto and Baldo, Guilherme},
 doi = {10.1016/bs.pmbts.2021.02.001},
 chapter = {Genome editing in lysosomal disorders}
}

@article{
 title = {Schizophreniform presentation and abrupt neurologic decline in a patient with late-onset mucopolysaccharidosis type IIIB},
 type = {article},
 year = {2021},
 pages = {199-204},
 volume = {31},
 websites = {https://journals.lww.com/10.1097/YPG.0000000000000294},
 month = {10},
 day = {3},
 id = {fab7e304-81e7-3a32-aa11-08a17720f3f7},
 created = {2021-12-30T11:50:06.375Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-12-30T11:50:06.375Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Montenegro, Yorran Hardman Araújo and Baldo, Guilherme and Giugliani, Roberto and Poswar, Fabiano de Oliveira and Sobrinho, Ruy Pires de Oliveira and Steiner, Carlos Eduardo},
 doi = {10.1097/YPG.0000000000000294},
 journal = {Psychiatric Genetics},
 number = {5}
}

@article{
 title = {Clinical trials for genetic diseases in Latin America},
 type = {article},
 year = {2021},
 pages = {381-387},
 volume = {187},
 websites = {https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31934},
 month = {9},
 day = {3},
 id = {ffb3e99a-61a5-327e-bf97-192c9216a12f},
 created = {2021-12-30T11:50:06.375Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-12-30T11:50:06.375Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Silva, Larissa Pozzebon and Zambrano, Marina Bauer and Pedrini, Diane Bressan and Saute, Jonas Alex Morales and Giugliani, Roberto},
 doi = {10.1002/ajmg.c.31934},
 journal = {American Journal of Medical Genetics Part C: Seminars in Medical Genetics},
 number = {3}
}

@article{
 title = {Novel AHDC1 Gene Mutation in a Brazilian Individual: Implications of Xia-Gibbs Syndrome},
 type = {article},
 year = {2020},
 keywords = {Exome sequencing,Intellectual disability,Neurodevelopmental disorders,Novel mutation,Sanger sequencing},
 pages = {24-29},
 volume = {11},
 websites = {https://www.karger.com/Article/FullText/505843},
 month = {2},
 day = {1},
 id = {b6aa3f71-0e3a-3ca6-bf1e-6a468664753e},
 created = {2020-02-12T03:23:09.776Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:57.913Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Xia-Gibbs syndrome (XGS) is a rare neurological disorder characterized by global developmental delay, hypotonia, intellectual disability, seizures, and sleep apnea. XGS is defined by monoallelic pathogenic variants in AHDC1. In this study, we identified a Brazilian patient carrying a likely de novo AHDC1 nonsense mutation (c.451C>T; p.Arg151∗) which was absent in both parents. All disease-causative variants already associated with XGS have been reviewed and the mutation described here corresponds to the closest one to the N-terminal region. Our findings were discussed based on the suggested genotype-phenotype correlation of the disease.},
 bibtype = {article},
 author = {Cardoso-Dos-Santos, Augusto C. and Oliveira Silva, Thiago and Silveira Faccini, Anderson and Woycinck Kowalski, Thayne and Bertoli-Avella, Aida and Morales Saute, Jonas A. and Schuler-Faccini, Lavinia and De Oliveira Poswar, Fabiano},
 doi = {10.1159/000505843},
 journal = {Molecular Syndromology},
 number = {1}
}

Xia-Gibbs syndrome (XGS) is a rare neurological disorder characterized by global developmental delay, hypotonia, intellectual disability, seizures, and sleep apnea. XGS is defined by monoallelic pathogenic variants in AHDC1. In this study, we identified a Brazilian patient carrying a likely de novo AHDC1 nonsense mutation (c.451C>T; p.Arg151∗) which was absent in both parents. All disease-causative variants already associated with XGS have been reviewed and the mutation described here corresponds to the closest one to the N-terminal region. Our findings were discussed based on the suggested genotype-phenotype correlation of the disease.

@article{
 title = {Quantification of glycosaminoglycans by liquid chromatography tandem mass spectrometry is a useful tool for screening of GlcNAc-phosphotransferase deficient patients},
 type = {article},
 year = {2020},
 pages = {S102},
 volume = {129},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719219311047},
 month = {2},
 id = {7ea754a2-b874-314d-b80c-70d310e579a4},
 created = {2020-02-15T13:12:03.057Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:52.723Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Ludwig, Nataniel and Kubaski, Francyne and Sperb-Ludwig, Fernanda and Burin, Maira Graeff and Silva, Thiago Oliveira and de Oliveira Poswar, Fabiano and Souza, Carolina Fischinger Moura and Giugliani, Roberto and Schwartz, Ida V.D.},
 doi = {10.1016/j.ymgme.2019.11.260},
 journal = {Molecular Genetics and Metabolism},
 number = {2}
}

@article{
 title = {Results from a phase 2 trial of a blood-brain barrier penetrating enzyme (JR-141) in patients with MPS II in Brazil},
 type = {article},
 year = {2020},
 pages = {S63},
 volume = {129},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719219309916},
 month = {2},
 id = {41c5b338-f0ab-30af-a9b5-1ef424a6ce9c},
 created = {2020-02-15T13:13:01.381Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:54.223Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Mucopolysaccharidosis type II (MPS II, Hunter disease) is a rare, X-linked lysosomal disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. The current intravenous enzyme replacement therapy (ERT) does not cross the blood-brain barrier (BBB) and cannot address central nervous system (CNS) manifestations of the disease, thus a novel therapy effective for the CNS is needed. Intrathecal and intracerebroventricular ERT administration are being tested, but these are invasive alternatives. JR-141 is a fusion protein that consists of human IDS and anti-human transferrin receptor antibody, designed to penetrate the BBB. Here we present the results of a phase 2, open-label, randomized, parallel group study to evaluate safety and efficacy of JR-141. Twenty patients, including 7 naive patients without previous ERT, were enrolled and received weekly intravenous infusions of 1.0, 2.0, or 4.0 mg/kg JR-141 for 6 months. The heparan sulfate (HS) concentrations in cerebrospinal fluid decreased at week 13 and 26 from baseline, indicating the penetration of JR-141 through BBB. Cognitive function and adaptive behavior were stable or improved in some patients during the study. The positive systemic effects of JR-141 were also demonstrated by some parameters, e.g. the concentrations of glycosaminoglycans in serum and urine, and the liver and spleen volumes. Some patients presented infusion-associated reactions, none of which were severe. No patients discontinued the study due to the drug-related adverse events. Taken together, the treatment of MPS II patients with JR-141 was well tolerated up to 4.0 mg/kg/week, the intravenous administered drug was able to decrease the levels of HS in the CSF, and several efficacy signals were detected. All subjects who completed this study have been enrolled in the extension study, which will provide longitudinal data and further information on the effects of JR-141.<br/>Copyright &#xa9; 2019},
 bibtype = {article},
 author = {Giugliani, Roberto and Martins, Ana Maria and Zambrano, Marina and Poswar, Fabiano and de Boer, Ana Paula and Sato, Yuji and Tanizawa, Kazunori and Yamamoto, Tatsuyoshi and So, Sairei and Yamaoka, Mariko and Kobayashi, Minako},
 doi = {10.1016/j.ymgme.2019.11.147},
 journal = {Molecular Genetics and Metabolism},
 number = {2}
}

Mucopolysaccharidosis type II (MPS II, Hunter disease) is a rare, X-linked lysosomal disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. The current intravenous enzyme replacement therapy (ERT) does not cross the blood-brain barrier (BBB) and cannot address central nervous system (CNS) manifestations of the disease, thus a novel therapy effective for the CNS is needed. Intrathecal and intracerebroventricular ERT administration are being tested, but these are invasive alternatives. JR-141 is a fusion protein that consists of human IDS and anti-human transferrin receptor antibody, designed to penetrate the BBB. Here we present the results of a phase 2, open-label, randomized, parallel group study to evaluate safety and efficacy of JR-141. Twenty patients, including 7 naive patients without previous ERT, were enrolled and received weekly intravenous infusions of 1.0, 2.0, or 4.0 mg/kg JR-141 for 6 months. The heparan sulfate (HS) concentrations in cerebrospinal fluid decreased at week 13 and 26 from baseline, indicating the penetration of JR-141 through BBB. Cognitive function and adaptive behavior were stable or improved in some patients during the study. The positive systemic effects of JR-141 were also demonstrated by some parameters, e.g. the concentrations of glycosaminoglycans in serum and urine, and the liver and spleen volumes. Some patients presented infusion-associated reactions, none of which were severe. No patients discontinued the study due to the drug-related adverse events. Taken together, the treatment of MPS II patients with JR-141 was well tolerated up to 4.0 mg/kg/week, the intravenous administered drug was able to decrease the levels of HS in the CSF, and several efficacy signals were detected. All subjects who completed this study have been enrolled in the extension study, which will provide longitudinal data and further information on the effects of JR-141.
Copyright © 2019

@article{
 title = {A minor correction to the variant nomenclature (e-letter)},
 type = {article},
 year = {2020},
 id = {49019ae4-4700-3103-a604-42d1f3aaf085},
 created = {2020-03-17T19:36:18.360Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:55.554Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {e-letter to the editorial "Fabry cardiomyopathy: missing links from genotype to phenotype".
Available at: https://heart.bmj.com/content/early/2020/01/16/heartjnl-2019-316143.responses#a-minor-correction-to-the-variant-nomenclature},
 bibtype = {article},
 author = {Poswar, F. O},
 doi = {https://heart.bmj.com/content/early/2020/01/16/heartjnl-2019-316143.responses#a-minor-correction-to-the-variant-nomenclature},
 journal = {Heart}
}

e-letter to the editorial "Fabry cardiomyopathy: missing links from genotype to phenotype". Available at: https://heart.bmj.com/content/early/2020/01/16/heartjnl-2019-316143.responses#a-minor-correction-to-the-variant-nomenclature

@article{
 title = {Mucopolysaccharidosis type I},
 type = {article},
 year = {2020},
 keywords = {Enzyme replacement therapy,Glycosaminoglycans,Hematopoietic stem cell transplantation,Hurler syndrome,Hurler-Scheie syndrome,Mucopolysaccharidosis type I,Scheie syndrome},
 pages = {161},
 volume = {10},
 websites = {https://www.mdpi.com/2075-4418/10/3/161},
 month = {3},
 day = {16},
 id = {90a6a3be-74a2-3ef5-a3a0-6d1ea7a8e5f1},
 created = {2020-03-17T19:59:36.965Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:54.434Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of α-l-iduronidase, leading to the storage of dermatan and heparan sulfate. There is a broad phenotypical spectrum with the presence or absence of neurological impairment. The classical form is known as Hurler syndrome, the intermediate form as Hurler-Scheie, and the most attenuated form is known as Scheie syndrome. Phenotype seems to be largely influenced by genotype. Patients usually develop several somatic symptoms such as abdominal hernias, extensive dermal melanocytosis, thoracolumbar kyphosis odontoid dysplasia, arthropathy, coxa valga and genu valgum, coarse facial features, respiratory and cardiac impairment. The diagnosis is based on the quantification of α-l-iduronidase coupled with glycosaminoglycan analysis and gene sequencing. Guidelines for treatment recommend hematopoietic stem cell transplantation for young Hurler patients (usually at less than 30 months of age). Intravenous enzyme replacement is approved and is the standard of care for attenuated-Hurler-Scheie and Scheie-forms (without cognitive impairment) and for the late-diagnosed severe-Hurler-cases. Intrathecal enzyme replacement therapy is under evaluation, but it seems to be safe and effective. Other therapeutic approaches such as gene therapy, gene editing, stop codon read through, and therapy with small molecules are under development. Newborn screening is now allowing the early identification of MPS I patients, who can then be treated within their first days of life, potentially leading to a dramatic change in the disease's progression. Supportive care is very important to improve quality of life and might include several surgeries throughout the life course.},
 bibtype = {article},
 author = {Kubaski, Francyne and de Oliveira Poswar, Fabiano and Michelin-Tirelli, Kristiane and da Silveira Matte, Ursula and Horovitz, Dafne D. and Barth, Anneliese Lopes and Baldo, Guilherme and Vairo, Filippo and Giugliani, Roberto},
 doi = {10.3390/diagnostics10030161},
 journal = {Diagnostics},
 number = {3}
}

Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of α-l-iduronidase, leading to the storage of dermatan and heparan sulfate. There is a broad phenotypical spectrum with the presence or absence of neurological impairment. The classical form is known as Hurler syndrome, the intermediate form as Hurler-Scheie, and the most attenuated form is known as Scheie syndrome. Phenotype seems to be largely influenced by genotype. Patients usually develop several somatic symptoms such as abdominal hernias, extensive dermal melanocytosis, thoracolumbar kyphosis odontoid dysplasia, arthropathy, coxa valga and genu valgum, coarse facial features, respiratory and cardiac impairment. The diagnosis is based on the quantification of α-l-iduronidase coupled with glycosaminoglycan analysis and gene sequencing. Guidelines for treatment recommend hematopoietic stem cell transplantation for young Hurler patients (usually at less than 30 months of age). Intravenous enzyme replacement is approved and is the standard of care for attenuated-Hurler-Scheie and Scheie-forms (without cognitive impairment) and for the late-diagnosed severe-Hurler-cases. Intrathecal enzyme replacement therapy is under evaluation, but it seems to be safe and effective. Other therapeutic approaches such as gene therapy, gene editing, stop codon read through, and therapy with small molecules are under development. Newborn screening is now allowing the early identification of MPS I patients, who can then be treated within their first days of life, potentially leading to a dramatic change in the disease's progression. Supportive care is very important to improve quality of life and might include several surgeries throughout the life course.

@article{
 title = {Diagnosis of mucopolysaccharidoses},
 type = {article},
 year = {2020},
 keywords = {Enzyme replacement therapy,Glycosaminoglycans,Mucopolysaccharidoses,Newborn screening,Tandem mass spectrometry},
 pages = {172},
 volume = {10},
 month = {3},
 publisher = {MDPI AG},
 day = {22},
 id = {22bd5682-5c1c-38f0-ae38-fd26b342aa69},
 created = {2020-04-22T03:20:35.373Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-06-05T01:55:07.667Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {2fde94ea-60c9-4695-8b22-7e026d01c478,b7782481-2ce8-4db1-8d76-f8d0a0dd50ed},
 private_publication = {false},
 abstract = {The mucopolysaccharidoses (MPSs) include 11 different conditions caused by specific enzyme deficiencies in the degradation pathway of glycosaminoglycans (GAGs). Although most MPS types present increased levels of GAGs in tissues, including blood and urine, diagnosis is challenging as specific enzyme assays are needed for the correct diagnosis. Enzyme assays are usually performed in blood, with some samples (as leukocytes) providing a final diagnosis, while others (such as dried blood spots) still being considered as screening methods. The identification of variants in the specific genes that encode each MPS-related enzyme is helpful for diagnosis confirmation (when needed), carrier detection, genetic counseling, prenatal diagnosis (preferably in combination with enzyme assays) and phenotype prediction. Although the usual diagnostic flow in high-risk patients starts with the measurement of urinary GAGs, it continues with specific enzyme assays and is completed with mutation identification; there is a growing trend to have genotype-based investigations performed at the beginning of the investigation. In such cases, confirmation of pathogenicity of the variants identified should be confirmed by measurement of enzyme activity and/or identification and/or quantification of GAG species. As there is a growing number of countries performing newborn screening for MPS diseases, the investigation of a low enzyme activity by the measurement of GAG species concentration and identification of gene mutations in the same DBS sample is recommended before the suspicion of MPS is taken to the family. With specific therapies already available for most MPS patients, and with clinical trials in progress for many conditions, the specific diagnosis of MPS as early as possible is becoming increasingly necessary. In this review, we describe traditional and the most up to date diagnostic methods for mucopolysaccharidoses.},
 bibtype = {article},
 author = {Kubaski, Francyne and De Oliveira Poswar, Fabiano and Michelin-Tirelli, Kristiane and Burin, Maira Grae and Rojas-Málaga, Diana and Brusius-Facchin, Ana Carolina and Leistner-Segal, Sandra and Giugliani, Roberto},
 doi = {10.3390/diagnostics10030172},
 journal = {Diagnostics},
 number = {3}
}

The mucopolysaccharidoses (MPSs) include 11 different conditions caused by specific enzyme deficiencies in the degradation pathway of glycosaminoglycans (GAGs). Although most MPS types present increased levels of GAGs in tissues, including blood and urine, diagnosis is challenging as specific enzyme assays are needed for the correct diagnosis. Enzyme assays are usually performed in blood, with some samples (as leukocytes) providing a final diagnosis, while others (such as dried blood spots) still being considered as screening methods. The identification of variants in the specific genes that encode each MPS-related enzyme is helpful for diagnosis confirmation (when needed), carrier detection, genetic counseling, prenatal diagnosis (preferably in combination with enzyme assays) and phenotype prediction. Although the usual diagnostic flow in high-risk patients starts with the measurement of urinary GAGs, it continues with specific enzyme assays and is completed with mutation identification; there is a growing trend to have genotype-based investigations performed at the beginning of the investigation. In such cases, confirmation of pathogenicity of the variants identified should be confirmed by measurement of enzyme activity and/or identification and/or quantification of GAG species. As there is a growing number of countries performing newborn screening for MPS diseases, the investigation of a low enzyme activity by the measurement of GAG species concentration and identification of gene mutations in the same DBS sample is recommended before the suspicion of MPS is taken to the family. With specific therapies already available for most MPS patients, and with clinical trials in progress for many conditions, the specific diagnosis of MPS as early as possible is becoming increasingly necessary. In this review, we describe traditional and the most up to date diagnostic methods for mucopolysaccharidoses.

@article{
 title = {Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study},
 type = {article},
 year = {2020},
 pages = {594-605},
 volume = {8},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S2213858720301534},
 month = {7},
 id = {91505e2c-4f0e-3f25-9ed7-518c3e43486d},
 created = {2020-06-17T01:04:01.022Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:51.097Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1–3 years (defined as a bodyweight-for-age Z score <–2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. Findings: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3–61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76–8·34; log-rank test p=0·0041). Patients who were underweight during age 1–3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26–17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. Interpretation: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies. Funding: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.},
 bibtype = {article},
 author = {Groeneweg, Stefan and van Geest, Ferdy S. and Abacı, Ayhan and Alcantud, Alberto and Ambegaonkar, Gautem P. and Armour, Christine M. and Bakhtiani, Priyanka and Barca, Diana and Bertini, Enrico S. and van Beynum, Ingrid M. and Brunetti-Pierri, Nicola and Bugiani, Marianna and Cappa, Marco and Cappuccio, Gerarda and Castellotti, Barbara and Castiglioni, Claudia and Chatterjee, Krishna and de Coo, Irenaeus F.M. and Coutant, Régis and Craiu, Dana and Crock, Patricia and DeGoede, Christian and Demir, Korcan and Dica, Alice and Dimitri, Paul and Dolcetta-Capuzzo, Anna and Dremmen, Marjolein H.G. and Dubey, Rachana and Enderli, Anina and Fairchild, Jan and Gallichan, Jonathan and George, Belinda and Gevers, Evelien F. and Hackenberg, Annette and Halász, Zita and Heinrich, Bianka and Huynh, Tony and Kłosowska, Anna and van der Knaap, Marjo S. and van der Knoop, Marieke M. and Konrad, Daniel and Koolen, David A. and Krude, Heiko and Lawson-Yuen, Amy and Lebl, Jan and Linder-Lucht, Michaela and Lorea, Cláudia F. and Lourenço, Charles M. and Lunsing, Roelineke J. and Lyons, Greta and Malikova, Jana and Mancilla, Edna E. and McGowan, Anne and Mericq, Veronica and Lora, Felipe M. and Moran, Carla and Müller, Katalin E. and Oliver-Petit, Isabelle and Paone, Laura and Paul, Praveen G. and Polak, Michel and Porta, Francesco and Poswar, Fabiano O. and Reinauer, Christina and Rozenkova, Klara and Menevse, Tuba S. and Simm, Peter and Simon, Anna and Singh, Yogen and Spada, Marco and van der Spek, Jet and Stals, Milou A.M. and Stoupa, Athanasia and Subramanian, Gopinath M. and Tonduti, Davide and Turan, Serap and den Uil, Corstiaan A. and Vanderniet, Joel and van der Walt, Adri and Wémeau, Jean Louis and Wierzba, Jolante and de Wit, Marie Claire Y. and Wolf, Nicole I. and Wurm, Michael and Zibordi, Federica and Zung, Amnon and Zwaveling-Soonawala, Nitash and Visser, W. Edward},
 doi = {10.1016/S2213-8587(20)30153-4},
 journal = {The Lancet Diabetes and Endocrinology},
 number = {7}
}

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1–3 years (defined as a bodyweight-for-age Z score <–2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. Findings: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3–61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76–8·34; log-rank test p=0·0041). Patients who were underweight during age 1–3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26–17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. Interpretation: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies. Funding: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.

@article{
 title = {Therapeutic Options for Mucopolysaccharidosis II (Hunter Disease)},
 type = {article},
 year = {2020},
 pages = {5100-5109},
 volume = {26},
 websites = {https://www.eurekaselect.com/184105/article},
 month = {7},
 day = {24},
 id = {72baab0e-2ab6-3079-86dc-3d0b7c1acf2a},
 created = {2020-10-29T02:23:24.460Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:51.758Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Kubaski, Francyne and Vairo, Filippo and Baldo, Guilherme and de Oliveira Poswar, Fabiano and Corte, Amauri Dalla and Giugliani, Roberto},
 doi = {10.2174/1381612826666200724161504},
 journal = {Current Pharmaceutical Design},
 number = {40}
}

@article{
 title = {Precision medicine for lysosomal disorders},
 type = {article},
 year = {2020},
 keywords = {Enzyme replacement therapy,Gene therapy,Lysosomal diseases,Pharmacological chaperones,Precision medicine},
 pages = {1-24},
 volume = {10},
 websites = {https://www.mdpi.com/2218-273X/10/8/1110},
 month = {7},
 day = {26},
 id = {89a01fe2-6643-3b2c-bf9c-6916f6e60d5d},
 created = {2020-10-29T02:24:23.462Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:54.030Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Precision medicine (PM) is an emerging approach for disease treatment and prevention that accounts for the individual variability in the genes, environment, and lifestyle of each person. Lysosomal diseases (LDs) are a group of genetic metabolic disorders that include approximately 70 monogenic conditions caused by a defect in lysosomal function. LDs may result from primary lysosomal enzyme deficiencies or impairments in membrane-associated proteins, lysosomal enzyme activators, or modifiers that affect lysosomal function. LDs are heterogeneous disorders, and the phenotype of the affected individual depends on the type of substrate and where it accumulates, which may be impacted by the type of genetic change and residual enzymatic activity. LDs are individually rare, with a combined incidence of approximately 1:4000 individuals. Specific therapies are already available for several LDs, and many more are in development. Early identification may enable disease course prediction and a specific intervention, which is very important for clinical outcome. Driven by advances in omics technology, PM aims to provide the most appropriate management for each patient based on the disease susceptibility or treatment response predictions for specific subgroups. In this review, we focused on the emerging diagnostic technologies that may help to optimize the management of each LD patient and the therapeutic options available, as well as in clinical developments that enable customized approaches to be selected for each subject, according to the principles of PM.},
 bibtype = {article},
 author = {Vairo, Filippo Pinto E. and Málaga, Diana Rojas and Kubaski, Francyne and de Souza, Carolina Fischinger Moura and Poswar, Fabiano de Oliveira and Baldo, Guilherme and Giugliani, Roberto},
 doi = {10.3390/biom10081110},
 journal = {Biomolecules},
 number = {8}
}

Precision medicine (PM) is an emerging approach for disease treatment and prevention that accounts for the individual variability in the genes, environment, and lifestyle of each person. Lysosomal diseases (LDs) are a group of genetic metabolic disorders that include approximately 70 monogenic conditions caused by a defect in lysosomal function. LDs may result from primary lysosomal enzyme deficiencies or impairments in membrane-associated proteins, lysosomal enzyme activators, or modifiers that affect lysosomal function. LDs are heterogeneous disorders, and the phenotype of the affected individual depends on the type of substrate and where it accumulates, which may be impacted by the type of genetic change and residual enzymatic activity. LDs are individually rare, with a combined incidence of approximately 1:4000 individuals. Specific therapies are already available for several LDs, and many more are in development. Early identification may enable disease course prediction and a specific intervention, which is very important for clinical outcome. Driven by advances in omics technology, PM aims to provide the most appropriate management for each patient based on the disease susceptibility or treatment response predictions for specific subgroups. In this review, we focused on the emerging diagnostic technologies that may help to optimize the management of each LD patient and the therapeutic options available, as well as in clinical developments that enable customized approaches to be selected for each subject, according to the principles of PM.

@article{
 title = {Cardiovascular findings in classic homocystinuria},
 type = {article},
 year = {2020},
 keywords = {Cardiovascular findings,Classic Homocystinuria,Cystathionine β-synthase deficiency,Echocardiogram,Electrocardiogram},
 pages = {1-5},
 volume = {25},
 id = {7ec9e4c0-9f07-3a2f-bb85-554df067d462},
 created = {2021-01-16T15:40:25.375Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-01-16T15:42:24.767Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: describe cardiovascular findings from echocardiograms and electrocardiograms in patients with Classic Homocystinuria Methods: this retrospective exploratory study evaluated fourteen subjects with Classic Homocystinuria (median age = 27.3 years; male n = 8, B6-non-responsive n = 9 patients), recruited by convenience sampling from patients seen Hospital de Clínicas de Porto Alegre (Brazil), between January 1997 and July 2020. Data on clinical findings, echocardiogram and electrocardiogram were retrieved from medical records. Results: Eight patients presented some abnormalities on echocardiogram (n = 6) or electrocardiogram (n = 5). The most frequent finding was mild tricuspid regurgitation (n = 3), followed by mitral valve prolapse, mild mitral regurgitation, enlarged left atrium and aortic valve sclerosis (n = 2 patients each). Aortic root ectasia was found in one patient. Venous thrombosis was reported in six patients: deep vein thrombosis of lower limbs (n = 3), ischaemic stroke (n = 1), cerebral venous sinus thrombosis (n = 1) and pulmonary vein thrombosis (n = 1). Conclusion: mild valvulopathies seen to be common in patients with Classic Homocystinuria, but more studies regarding echocardiogram and electrocardiogram in this population are needed to draw absolute conclusions.},
 bibtype = {article},
 author = {Kalil, Marco Antônio Baptista and Donis, Karina Carvalho and Poswar, Fabiano de Oliveira and dos Santos, Bruna Bento and Santos, Ângela Barreto Santiago and Schwartz, Ida Vanessa Doederlein},
 doi = {10.1016/j.ymgmr.2020.100693},
 journal = {Molecular Genetics and Metabolism Reports},
 number = {November}
}

Objective: describe cardiovascular findings from echocardiograms and electrocardiograms in patients with Classic Homocystinuria Methods: this retrospective exploratory study evaluated fourteen subjects with Classic Homocystinuria (median age = 27.3 years; male n = 8, B6-non-responsive n = 9 patients), recruited by convenience sampling from patients seen Hospital de Clínicas de Porto Alegre (Brazil), between January 1997 and July 2020. Data on clinical findings, echocardiogram and electrocardiogram were retrieved from medical records. Results: Eight patients presented some abnormalities on echocardiogram (n = 6) or electrocardiogram (n = 5). The most frequent finding was mild tricuspid regurgitation (n = 3), followed by mitral valve prolapse, mild mitral regurgitation, enlarged left atrium and aortic valve sclerosis (n = 2 patients each). Aortic root ectasia was found in one patient. Venous thrombosis was reported in six patients: deep vein thrombosis of lower limbs (n = 3), ischaemic stroke (n = 1), cerebral venous sinus thrombosis (n = 1) and pulmonary vein thrombosis (n = 1). Conclusion: mild valvulopathies seen to be common in patients with Classic Homocystinuria, but more studies regarding echocardiogram and electrocardiogram in this population are needed to draw absolute conclusions.

@article{
 title = {Clinical Features and Outcomes in Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE) Syndrome: Before and After JAK-inhibition},
 type = {article},
 year = {2020},
 pages = {44-47},
 volume = {72 MA  - 0},
 id = {b947d492-6130-31ee-9189-c32163b90108},
 created = {2023-05-05T21:36:02.719Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2023-05-05T21:36:48.190Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 source_type = {JOUR},
 private_publication = {false},
 bibtype = {article},
 author = {Torreggiani, S and Pillet, P and Poswar, F D and Kozlova, A and Shcherbina, A and de Guzman, M and Mitchell, J and Sanchez, G A M and Townsend, K and Johnson, K and de Jesus, A A and Goldbach-Mansky, R},
 journal = {ARTHRITIS & RHEUMATOLOGY}
}

@article{
 title = {6th Update on Fabry Disease: Biomarkers, Progression and Treatment Opportunities},
 type = {article},
 year = {2019},
 pages = {159-194},
 volume = {142},
 id = {e35ba9c0-cc53-3e8f-bb85-e6fc3ed1c9a4},
 created = {2020-02-15T14:01:29.224Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:52.975Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Fabiano de Oliveira Poswar, undefined and Cristina Brinckmann Oliveira Netto, undefined and Roberto Giugliani, undefined},
 doi = {10.1159/000500644},
 journal = {Nephron},
 number = {3}
}

@article{
 title = {Neurological manifestations of lysosomal disorders and emerging therapies targeting the CNS},
 type = {article},
 year = {2018},
 pages = {56-68},
 volume = {2},
 id = {1c3b9c4b-eafe-3c67-9ab5-2b2254a8069c},
 created = {2018-01-16T17:29:07.367Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:16.544Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {2fde94ea-60c9-4695-8b22-7e026d01c478,d0264d5b-4653-45f8-b3a9-d49691668045},
 private_publication = {false},
 abstract = {Lysosomal disorders have been an area of interest since intravenous enzyme replacement therapy was successfully introduced for the treatment of Gaucher's disease in the early 1990s. This treatment approach has also been developed for several other lysosomal disorders, including Fabry's disease, Pompe's disease, lysosomal acid lipase deficiency, and five types of mucopolysaccharidosis. Despite the benefits of enzyme replacement therapy, it has limitations—most importantly, its ineffectiveness in treating the neurological components of lysosomal disorders, as only a small proportion of recombinant enzymes can cross the blood–brain barrier. Development of strategies to improve drug delivery to the CNS is now the primary focus in lysosomal disorder research. This Review discusses the neurological manifestations and emerging therapies for the CNS component of these diseases. The therapies in development (which are now in phase 1 or phase 2 clinical trials) might be for specific lysosomal disorders (enzyme replacement therapy via intrathecal or intracerebroventricular routes or with fusion proteins, or gene therapy) or applicable to more than one lysosomal disorder (haemopoietic stem cell transplantation, pharmacological chaperones, substrate reduction therapy, or stop codon readthrough). The combination of early diagnosis with effective therapies should change the outlook for patients with lysosomal disorders with neurological involvement in the next 5–10 years.},
 bibtype = {article},
 author = {Giugliani, Roberto and Vairo, Filippo and Kubaski, Francyne and Poswar, Fabiano and Riegel, Mariluce and Baldo, Guilherme and Saute, Jonas Alex},
 doi = {10.1016/S2352-4642(17)30087-1},
 journal = {The Lancet Child and Adolescent Health},
 number = {1}
}

Lysosomal disorders have been an area of interest since intravenous enzyme replacement therapy was successfully introduced for the treatment of Gaucher's disease in the early 1990s. This treatment approach has also been developed for several other lysosomal disorders, including Fabry's disease, Pompe's disease, lysosomal acid lipase deficiency, and five types of mucopolysaccharidosis. Despite the benefits of enzyme replacement therapy, it has limitations—most importantly, its ineffectiveness in treating the neurological components of lysosomal disorders, as only a small proportion of recombinant enzymes can cross the blood–brain barrier. Development of strategies to improve drug delivery to the CNS is now the primary focus in lysosomal disorder research. This Review discusses the neurological manifestations and emerging therapies for the CNS component of these diseases. The therapies in development (which are now in phase 1 or phase 2 clinical trials) might be for specific lysosomal disorders (enzyme replacement therapy via intrathecal or intracerebroventricular routes or with fusion proteins, or gene therapy) or applicable to more than one lysosomal disorder (haemopoietic stem cell transplantation, pharmacological chaperones, substrate reduction therapy, or stop codon readthrough). The combination of early diagnosis with effective therapies should change the outlook for patients with lysosomal disorders with neurological involvement in the next 5–10 years.

@article{
 title = {Intrathecal/Intracerebroventricular enzyme replacement therapy for the mucopolysaccharidoses: efficacy, safety, and prospects},
 type = {article},
 year = {2018},
 keywords = {Mucopolysaccharidoses,blood–brain barrier,enzyme replacement therapy,glycosaminoglycans,intracerebroventricular,intrathecal},
 pages = {403-411},
 volume = {6},
 websites = {https://doi.org/10.1080/21678707.2018.1487838},
 month = {7},
 day = {3},
 id = {a48e7038-931b-3a35-b211-7057d8f11662},
 created = {2018-08-14T04:28:28.955Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:57.635Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: The mucopolysaccharidoses (MPS) are lysosomal storage diseases (LSDs) caused by the deficiency of an enzyme involved in the breakdown of glycosaminoglycans (GAGs), which leads to GAG storage and results in multisystemic manifestations. In some of the 11 MPS types, patients could have cognitive involvement and/or secondary neurologic manifestations. Intravenous enzyme replacement therapy (ERT), already approved for several MPS types, is not able to cross the blood–brain barrier and does not address the neurologic manifestations present in most MPS types. Intrathecal (IT) or intracerebroventricular (ICV) administration of the enzyme directly into the cerebrospinal fluid (CSF) has been proposed and experienced in clinical trials and in single cases. Areas covered: This paper briefly summarizes the development of ERT to treat LSDs, particularly MPS, the technical aspects related to its CSF administration, the experience obtained so far with the IT and ICV use in several MPS types and provides an expert opinion on this subject. Expert opinion: Treatment of neuropathic MPS remains a challenge. The results of ongoing trials may bring IT and ICV administration of ERT to clinical use in the coming years, making it a therapeutic option for the treatment of neuronopathic patients in several MPS types.},
 bibtype = {article},
 author = {Giugliani, Roberto and Dalla Corte, Amauri and Poswar, Fabiano and Vanzella, Cláudia and Horovitz, Dafne and Riegel, Mariluce and Baldo, Guilherme and Vairo, Filippo},
 doi = {10.1080/21678707.2018.1487838},
 journal = {Expert Opinion on Orphan Drugs},
 number = {7}
}

Introduction: The mucopolysaccharidoses (MPS) are lysosomal storage diseases (LSDs) caused by the deficiency of an enzyme involved in the breakdown of glycosaminoglycans (GAGs), which leads to GAG storage and results in multisystemic manifestations. In some of the 11 MPS types, patients could have cognitive involvement and/or secondary neurologic manifestations. Intravenous enzyme replacement therapy (ERT), already approved for several MPS types, is not able to cross the blood–brain barrier and does not address the neurologic manifestations present in most MPS types. Intrathecal (IT) or intracerebroventricular (ICV) administration of the enzyme directly into the cerebrospinal fluid (CSF) has been proposed and experienced in clinical trials and in single cases. Areas covered: This paper briefly summarizes the development of ERT to treat LSDs, particularly MPS, the technical aspects related to its CSF administration, the experience obtained so far with the IT and ICV use in several MPS types and provides an expert opinion on this subject. Expert opinion: Treatment of neuropathic MPS remains a challenge. The results of ongoing trials may bring IT and ICV administration of ERT to clinical use in the coming years, making it a therapeutic option for the treatment of neuronopathic patients in several MPS types.

@article{
 title = {Neurocognitive and somatic stabilization in pediatric patients with severe Mucopolysaccharidosis Type i after 52 weeks of intravenous brain-penetrating insulin receptor antibody-iduronidase fusion protein (valanafusp alpha): An open label phase 1-2 trial},
 type = {article},
 year = {2018},
 keywords = {Blood-brain barrier,Efficacy,Iduronidase,Insulin receptor,Mucopolysaccharidosis Type I,Open label clinical trial,Safety},
 volume = {13},
 websites = {http://www.scopus.com/inward/record.url?eid=2-s2.0-85049516297&partnerID=MN8TOARS},
 id = {8fecf73f-7d95-3b81-b45f-c74d3c388eb0},
 created = {2018-08-14T04:28:29.024Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:58.155Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Mucopolysaccharidosis (MPS) Type I (MPSI) is caused by mutations in the gene encoding the lysosomal enzyme, α-L-iduronidase (IDUA), and a majority of patients present with severe neurodegeneration and cognitive impairment. Recombinant IDUA does not cross the blood-brain barrier (BBB). To enable BBB transport, IDUA was re-engineered as an IgG-IDUA fusion protein, valanafusp alpha, where the IgG domain targets the BBB human insulin receptor to enable transport of the enzyme into the brain. We report the results of a 52-week clinical trial on the safety and efficacy of valanafusp alpha in pediatric MPSI patients with cognitive impairment. In the phase I trial, 6 adults with attenuated MPSI were administered 0.3, 1, and 3 mg/kg doses of valanafusp alpha by intravenous (IV) infusion. In the phase II trial, 11 pediatric subjects, 2-15 years of age, were treated for 52 weeks with weekly IV infusions of valanafusp alpha at 1, 3, or 6 mg/kg. Assessments of adverse events, cognitive stabilization, and somatic stabilization were made. Outcomes at 52 weeks were compared to baseline. Results: Drug related adverse events included infusion related reactions, with an incidence of 1.7%, and transient hypoglycemia, with an incidence of 6.4%. The pediatric subjects had CNS involvement with a mean enrollment Development Quotient (DQ) of 36.1±7.1. The DQ, and the cortical grey matter volume of brain, were stabilized by valanafusp alpha treatment. Somatic manifestations were stabilized, or improved, based on urinary glycosaminoglycan levels, hepatic and spleen volumes, and shoulder range of motion. Conclusion: Clinical evidence of the cognitive and somatic stabilization indicates that valanafusp alpha is transported into both the CNS and into peripheral organs due to its dual targeting mechanism via the insulin receptor and the mannose 6-phosphate receptor. This novel fusion protein offers a pharmacologic approach to the stabilization of cognitive function in MPSI. Trial registration: Clinical Trials.Gov, NCT03053089. Retrospectively registered 9 February, 2017; Clinical Trials.Gov, NCT03071341. Registered 6 March, 2017.},
 bibtype = {article},
 author = {Giugliani, Roberto and Giugliani, Luciana and De Oliveira Poswar, Fabiano and Donis, Karina Carvalho and Corte, Amauri Dalla and Schmidt, Mathias and Boado, Ruben J. and Nestrasil, Igor and Nguyen, Carol and Chen, Steven and Pardridge, William M.},
 doi = {10.1186/s13023-018-0849-8},
 journal = {Orphanet Journal of Rare Diseases},
 number = {1}
}

Background: Mucopolysaccharidosis (MPS) Type I (MPSI) is caused by mutations in the gene encoding the lysosomal enzyme, α-L-iduronidase (IDUA), and a majority of patients present with severe neurodegeneration and cognitive impairment. Recombinant IDUA does not cross the blood-brain barrier (BBB). To enable BBB transport, IDUA was re-engineered as an IgG-IDUA fusion protein, valanafusp alpha, where the IgG domain targets the BBB human insulin receptor to enable transport of the enzyme into the brain. We report the results of a 52-week clinical trial on the safety and efficacy of valanafusp alpha in pediatric MPSI patients with cognitive impairment. In the phase I trial, 6 adults with attenuated MPSI were administered 0.3, 1, and 3 mg/kg doses of valanafusp alpha by intravenous (IV) infusion. In the phase II trial, 11 pediatric subjects, 2-15 years of age, were treated for 52 weeks with weekly IV infusions of valanafusp alpha at 1, 3, or 6 mg/kg. Assessments of adverse events, cognitive stabilization, and somatic stabilization were made. Outcomes at 52 weeks were compared to baseline. Results: Drug related adverse events included infusion related reactions, with an incidence of 1.7%, and transient hypoglycemia, with an incidence of 6.4%. The pediatric subjects had CNS involvement with a mean enrollment Development Quotient (DQ) of 36.1±7.1. The DQ, and the cortical grey matter volume of brain, were stabilized by valanafusp alpha treatment. Somatic manifestations were stabilized, or improved, based on urinary glycosaminoglycan levels, hepatic and spleen volumes, and shoulder range of motion. Conclusion: Clinical evidence of the cognitive and somatic stabilization indicates that valanafusp alpha is transported into both the CNS and into peripheral organs due to its dual targeting mechanism via the insulin receptor and the mannose 6-phosphate receptor. This novel fusion protein offers a pharmacologic approach to the stabilization of cognitive function in MPSI. Trial registration: Clinical Trials.Gov, NCT03053089. Retrospectively registered 9 February, 2017; Clinical Trials.Gov, NCT03071341. Registered 6 March, 2017.

@article{
 title = {Somatic effects of AGT-181 in patients with mucopolysaccharidosis I enrolled in a phase I/II clinical trial in Brazil},
 type = {article},
 year = {2018},
 pages = {S53},
 volume = {123},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719217309010},
 month = {2},
 id = {da5637fe-d267-3b5c-9b87-7673665778c2},
 created = {2020-02-15T13:14:10.273Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:56.557Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Giugliani, Luciana and Donis, Karina Carvalho and Poswar, Fabiano and Giugliani, Roberto and Boado, Ruben},
 doi = {10.1016/j.ymgme.2017.12.126},
 journal = {Molecular Genetics and Metabolism},
 number = {2}
}

@article{
 title = {Safety and clinical efficacy of AGT-181, a brain penetrating human insulin receptor antibody-iduronidase fusion protein, in a 26-week study with pediatric patients with mucopolysaccharidosis type I},
 type = {article},
 year = {2018},
 pages = {S54},
 volume = {123},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719217309034},
 month = {2},
 id = {bc31d112-1137-36da-8d9c-d6b5f95eb336},
 created = {2020-02-15T13:15:24.728Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:55.232Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Giugliani, Roberto and Giugliani, Luciana and Corte, Amauri Dalla and Poswar, Fabiano and Donis, Karina and Schmidt, Mathias and Hunt, Douglas and Boado, Ruben J. and Pardridge, William M.},
 doi = {10.1016/j.ymgme.2017.12.128},
 journal = {Molecular Genetics and Metabolism},
 number = {2}
}

@article{
 title = {Phase I and II clinical trials for the mucopolysaccharidoses},
 type = {article},
 year = {2017},
 keywords = {Clinical trials,enzyme replacement therapy,gene therapy,glycosaminoglycans,intrathecal therapy,mucopolysaccharidoses,stop-codon read through,substrate reduction therapy},
 pages = {1331-1340},
 volume = {26},
 id = {d3c880bb-633e-36f9-8014-6a8407a7f321},
 created = {2018-01-16T17:29:06.879Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:18.164Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {2fde94ea-60c9-4695-8b22-7e026d01c478,d0264d5b-4653-45f8-b3a9-d49691668045,912acba1-9ccd-4ebd-9e82-02f2ca91f7e1},
 private_publication = {false},
 abstract = {Introduction: The mucopolysaccharidoses are lysosomal diseases characterized by deficient activity of one of the enzymes that degrades glycosaminoglycans. Treatment options are limited; therefore, new treatments are under investigation. Areas covered: We review the medicinal products for the treatment of mucopolysaccharidoses that are currently being investigated in phase I and phase II clinical trials. Expert opinion: The number of alternatives to treat MPS diseases increased dramatically in an attempt to provide therapy options for orphan MPS diseases and to address the unmet needs of the MPS that already have a treatment available. Intravenous enzyme replacement therapy (ERT) with fusion proteins, intrathecal/intracerebroventricular (ICV) ERT and gene therapy are the most promising strategies addressing the CNS manifestations. Stop-codon read-through, although proposed only for patients with nonsense mutations, might be useful in all MPS types. Substrate reduction therapy could also play a role in any MPS type, as anti-inflammatory drugs are also being tested. This new generation of therapies is now in clinical development and should bring new hope to MPS patients. As cost and logistics remain major challenges, especially for low- and middle-income countries, the possibility of having a one-time treatment such as gene therapy is anxiously awaited by affected families and healthcare systems.},
 bibtype = {article},
 author = {Poswar, Fabiano and Baldo, Guilherme and Giugliani, Roberto},
 doi = {10.1080/13543784.2017.1397130},
 journal = {Expert Opinion on Investigational Drugs},
 number = {12}
}

Introduction: The mucopolysaccharidoses are lysosomal diseases characterized by deficient activity of one of the enzymes that degrades glycosaminoglycans. Treatment options are limited; therefore, new treatments are under investigation. Areas covered: We review the medicinal products for the treatment of mucopolysaccharidoses that are currently being investigated in phase I and phase II clinical trials. Expert opinion: The number of alternatives to treat MPS diseases increased dramatically in an attempt to provide therapy options for orphan MPS diseases and to address the unmet needs of the MPS that already have a treatment available. Intravenous enzyme replacement therapy (ERT) with fusion proteins, intrathecal/intracerebroventricular (ICV) ERT and gene therapy are the most promising strategies addressing the CNS manifestations. Stop-codon read-through, although proposed only for patients with nonsense mutations, might be useful in all MPS types. Substrate reduction therapy could also play a role in any MPS type, as anti-inflammatory drugs are also being tested. This new generation of therapies is now in clinical development and should bring new hope to MPS patients. As cost and logistics remain major challenges, especially for low- and middle-income countries, the possibility of having a one-time treatment such as gene therapy is anxiously awaited by affected families and healthcare systems.

@article{
 title = {An adaptation of particle swarm clustering applied in basal cell carcinoma, squamous cell carcinoma of the skin and actinic keratosis},
 type = {article},
 year = {2017},
 keywords = {Bioinformatics,Metastasis,Particle swarm clustering,Potential malignant lesion,Skin cancers},
 pages = {72-77},
 volume = {12},
 id = {3bb2c5ea-6b3e-31cf-bee2-a3daf863eb01},
 created = {2018-01-16T17:29:07.913Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:18.599Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction This study used the comparison of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC) and actinic keratosis (AK) to test a new method for data set clustering in the leader gene approach. Methods Genes related to BCC, SCC and AK, were identified in the databases: OMIM, Genecards and NCBI Gene. A network was built for BCC, SCC and AK using STRING. For each gene, a weighted number of links (WNL) was calculated based on the combined STRING scores. The genes were then clustered according to their WNL and TIS, using an adaptation of particle swarm clustering (PSC) or K-means clustering. Results A disagreement between K-means clustering and PSC was observed for both BCC and SCC. PSC suggested completed different leader genes to BCC and SCC. While K-means clustering indicated that CTNNB1 and TP53 were associated with BCC and SCC. In contrast, no differences in methods were observed to AK, which had the shorter network. TP53 was the only leader gene for AK. Conclusion In conclusion, the current study suggests that PSC is an interesting tool for clustering genes in bioinformatics analyses of prevalent diseases. K-means clustering should be used in the small network. The current study also suggests TP53 may play a central role for AK. Additionally, CTNNB1 seems to be related to BCC, while CTNNA1 is related to SCC},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Santos, Laércio Ives and Farias, Lucyana Conceição and Guimarães, Talita Antunes and Santos, Sérgio Henrique Souza and Jones, Kimberly Marie and de Paula, Alfredo Maurício Batista and Palhares, Reinaldo Martinez and D'Angelo, Marcos Flávio Silveira Vasconcelos and Guimarães, André Luiz Sena},
 doi = {10.1016/j.mgene.2017.01.007},
 journal = {Meta Gene}
}

Introduction This study used the comparison of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC) and actinic keratosis (AK) to test a new method for data set clustering in the leader gene approach. Methods Genes related to BCC, SCC and AK, were identified in the databases: OMIM, Genecards and NCBI Gene. A network was built for BCC, SCC and AK using STRING. For each gene, a weighted number of links (WNL) was calculated based on the combined STRING scores. The genes were then clustered according to their WNL and TIS, using an adaptation of particle swarm clustering (PSC) or K-means clustering. Results A disagreement between K-means clustering and PSC was observed for both BCC and SCC. PSC suggested completed different leader genes to BCC and SCC. While K-means clustering indicated that CTNNB1 and TP53 were associated with BCC and SCC. In contrast, no differences in methods were observed to AK, which had the shorter network. TP53 was the only leader gene for AK. Conclusion In conclusion, the current study suggests that PSC is an interesting tool for clustering genes in bioinformatics analyses of prevalent diseases. K-means clustering should be used in the small network. The current study also suggests TP53 may play a central role for AK. Additionally, CTNNB1 seems to be related to BCC, while CTNNA1 is related to SCC

@article{
 title = {Sanfilippo syndrome type B: a review of patients diagnosed by the MPS Brazil Network},
 type = {article},
 year = {2017},
 pages = {S45},
 volume = {120},
 month = {1},
 id = {11d8ffc7-f14b-3637-8bfc-e4ef93518dcf},
 created = {2018-08-14T04:28:28.975Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:57.698Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction: MPS Brazil Network (MBN) was created to improve diagnosis and management of MPS diseases in Brazil. So far, 1,297 MPS patients were identified, being 96 (7.4%) diagnosed as having MPS IIIB. <br/>Method(s): Data from the 84 Brazilian MPS IIIB patients were retrieved, in an attempt to draw a picture of the disease in the country. Data reviewed included: date of birth, date of diagnosis, Brazilian region of origin, gender, race, parental consanguinity and diagnostic hypothesis indicated by the referring physician. <br/>Result(s): From the 84 patients, 42 were female and 42 male. Age of patients at diagnosis was, in average, 7.7 years (median was 6.4 years; range from 0.6 to 25.5). Race was reported only for 15 patients, being 11 classified as White and 4 as African Brazilian. Information regarding parental consanguinity was reported for 40 patients (47%). Of these, 22 couples were not consanguineous and 18 were consanguineous. Regarding the region of patient origin, information was available for 82 patients: 37 (45%) patients came from Southeast region, 27 (34%) from the South region, 8 (10%) from the Northeast region, 7 (8%) from the Center-West region, and 3 (3%) from the North region. The most frequent diagnostic hypotheses indicated by the referring doctors were: MPS 27; MPS III 22; IEM 13; MPS I 12; MPS II 7; and MPS IIIB 6. <br/>Conclusion(s): The disease seems to be underdiagnosed in Brazil, at least in the Northeast, North and Center-West regions. Diagnosis in Brazil occurs late in the course of the disease, being a diagnostic suspicion raised more commonly only when somatic manifestations become apparent. There is a need to increase awareness of health professionals about the early manifestations of MPS IIIB, especially as specific therapies are being developed for this disease.},
 bibtype = {article},
 author = {Federhen, Andressa and Poswar, Fabiano Oliveira and Trapp, Franciele Barbosa and da Rosa, Heluísa Castagnino and Silva, Laysla Pedelhes and Rocha, Daniele Lima and Burin, Maira Graeff and Guidobono, Regis R and De Mari, Jurema F and Bitencourt, Fernanda and Leistner-Segal, Sandra and Facchin, Ana Carolina Brusius and Matte, Ursula Silveira and Giugliani, Roberto},
 doi = {10.1016/j.ymgme.2016.11.092},
 journal = {Molecular Genetics and Metabolism},
 number = {1-2}
}

Introduction: MPS Brazil Network (MBN) was created to improve diagnosis and management of MPS diseases in Brazil. So far, 1,297 MPS patients were identified, being 96 (7.4%) diagnosed as having MPS IIIB.
Method(s): Data from the 84 Brazilian MPS IIIB patients were retrieved, in an attempt to draw a picture of the disease in the country. Data reviewed included: date of birth, date of diagnosis, Brazilian region of origin, gender, race, parental consanguinity and diagnostic hypothesis indicated by the referring physician.
Result(s): From the 84 patients, 42 were female and 42 male. Age of patients at diagnosis was, in average, 7.7 years (median was 6.4 years; range from 0.6 to 25.5). Race was reported only for 15 patients, being 11 classified as White and 4 as African Brazilian. Information regarding parental consanguinity was reported for 40 patients (47%). Of these, 22 couples were not consanguineous and 18 were consanguineous. Regarding the region of patient origin, information was available for 82 patients: 37 (45%) patients came from Southeast region, 27 (34%) from the South region, 8 (10%) from the Northeast region, 7 (8%) from the Center-West region, and 3 (3%) from the North region. The most frequent diagnostic hypotheses indicated by the referring doctors were: MPS 27; MPS III 22; IEM 13; MPS I 12; MPS II 7; and MPS IIIB 6.
Conclusion(s): The disease seems to be underdiagnosed in Brazil, at least in the Northeast, North and Center-West regions. Diagnosis in Brazil occurs late in the course of the disease, being a diagnostic suspicion raised more commonly only when somatic manifestations become apparent. There is a need to increase awareness of health professionals about the early manifestations of MPS IIIB, especially as specific therapies are being developed for this disease.

@article{
 title = {Long-term restoration of alpha-L-iduronidase activity in fibroblasts from patients with mucopolysaccharidosis type I after non-viral gene transfer},
 type = {article},
 year = {2017},
 pages = {330-333},
 volume = {37},
 publisher = {Tikinet Edicao Ltda. - EPP},
 id = {6c8dd4d8-f4c6-3205-a265-cc231c84ba58},
 created = {2020-02-05T22:40:56.800Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:36:40.159Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {2fde94ea-60c9-4695-8b22-7e026d01c478,912acba1-9ccd-4ebd-9e82-02f2ca91f7e1},
 private_publication = {false},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Mayer, Fabiana Quoos and Burin, Maira and Matte, Ursula da Silveira and Giugliani, Roberto and Baldo, Guilherme},
 doi = {10.4322/2357-9730.74048},
 journal = {Clinical & Biomedical Research},
 number = {4}
}

@article{
 title = {Increasing demonstration of angiogenic markers in skin neoplastic lesions},
 type = {article},
 year = {2016},
 keywords = {Actinic keratosis,Basal cell carcinoma,Matrix metalloproteinase-2,Membrane-type matrix metalloproteinase 1,Skin cancer,Squamous cell carcinoma},
 pages = {101-105},
 volume = {212},
 id = {35a26b51-4be4-3c4f-9db6-20acc36440fd},
 created = {2018-01-16T17:29:07.492Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:18.566Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Background: Skin cancer represents the most common worldwide malignancy. Angiogenesis is an important factor in tumor growth and metastasis. Given these facts, the purpose of the current study was to compare the levels of angiogenic proteins in the context of the most common malignant and premalignant skin lesions. Methods: Immunohistochemistry of CD31, HIF1A, VEGFR1 and VEGFR2 was performed in basal cell carcinoma (BCC), actinic keratosis (AK) and squamous cell carcinoma of the skin (SCCS). Results: SCCS presented with increased levels of HIF1A, VEGFR1 and VEGFR2 in comparison to AK. In addition, SCCS also demonstrated increased levels of HIF1A to BCCLR or BCCHR. BCC presented with more vessels than AK. However, no correlation was observed among CD31, HIF1A, VEGFR1 and VEGFR2. Conclusions: SCCS presented with higher levels of HIF1A, VEGFR1 and VEGFR2, while BCC demonstrated an increased number of vessels in relation to AK. These data suggest that antiangiogenic therapy might be useful for skin cancer treatment.},
 bibtype = {article},
 author = {de Almeida, Carla Mendonça and de Jesus, Sabina Ferreira and Poswar, Fabiano de Oliveira and Gomes, Emisael Stênio Batista and Fraga, Carlos Alberto de Carvalho and Farias, Lucyana Conceição and Santos, Sérgio Henrique Souza and Feltenberger, John David and de Paula, Alfredo Maurício Batista and Guimarães, André Luiz Sena},
 doi = {10.1016/j.prp.2015.12.004},
 journal = {Pathology Research and Practice},
 number = {2}
}

Background: Skin cancer represents the most common worldwide malignancy. Angiogenesis is an important factor in tumor growth and metastasis. Given these facts, the purpose of the current study was to compare the levels of angiogenic proteins in the context of the most common malignant and premalignant skin lesions. Methods: Immunohistochemistry of CD31, HIF1A, VEGFR1 and VEGFR2 was performed in basal cell carcinoma (BCC), actinic keratosis (AK) and squamous cell carcinoma of the skin (SCCS). Results: SCCS presented with increased levels of HIF1A, VEGFR1 and VEGFR2 in comparison to AK. In addition, SCCS also demonstrated increased levels of HIF1A to BCCLR or BCCHR. BCC presented with more vessels than AK. However, no correlation was observed among CD31, HIF1A, VEGFR1 and VEGFR2. Conclusions: SCCS presented with higher levels of HIF1A, VEGFR1 and VEGFR2, while BCC demonstrated an increased number of vessels in relation to AK. These data suggest that antiangiogenic therapy might be useful for skin cancer treatment.

@article{
 title = {Adenosine deaminase 2 deficiency presenting as spastic paraplegia and systemic vasculitis},
 type = {article},
 year = {2016},
 pages = {818-820},
 volume = {263},
 id = {54017903-39ca-355d-bf29-dc7c18b0e8b9},
 created = {2018-01-16T17:29:07.810Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:05.265Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and da Fonseca, Raymundo Mesko Tomkowski and de Albuquerque, Leonardo Cordenonzi Pedroso and Zhou, Qing and Jardim, Laura Bannach and Monte, Thais Lampert and Aksentijevich, Ivona and Saute, Jonas Alex Morales},
 doi = {10.1007/s00415-016-8070-y},
 journal = {Journal of Neurology},
 number = {4}
}

@article{
 title = {Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and hurler syndrome},
 type = {article},
 year = {2016},
 keywords = {Adrenoleukodystrophy,Hematopoietic stem cell transplantation,Leukodystrophy,Metachromatic,Mucopolysaccharidosis I},
 pages = {953-966},
 volume = {74},
 id = {6ba40835-397d-369f-b71e-fa1c1fc08977},
 created = {2018-01-16T17:29:08.206Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:18.228Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Hematopoietic stem cell transplantation (HSCT) is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I-Hurler (MPS-IH), and X-linked cerebral adrenoleukodystrophy (CALD). Objective: To describe survival and neurological outcomes after HSCT for these disorders. Methods: Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Results: Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Conclusion: Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.},
 bibtype = {article},
 author = {Saute, Jonas Alex Morales and De Souza, Carolina Fischinger Moura and De Oliveira Poswar, Fabiano and Donis, Karina Carvalho and Campos, Lillian Gonçalves and Deyl, Adriana Vanessa Santini and Burin, Maira Graeff and Vargas, Carmen Regla and Da Silveira Matte, Ursula and Giugliani, Roberto and Saraiva-Pereira, Maria Luiza and Vedolin, Leonardo Modesti and Gregianin, Lauro José and Jardim, Laura Bannach},
 doi = {10.1590/0004-282x20160155},
 journal = {Arquivos de Neuro-Psiquiatria},
 number = {12}
}

Hematopoietic stem cell transplantation (HSCT) is the only available treatment for the neurological involvement of disorders such as late-onset metachromatic leukodystrophy (MLD), mucopolysaccharidosis type I-Hurler (MPS-IH), and X-linked cerebral adrenoleukodystrophy (CALD). Objective: To describe survival and neurological outcomes after HSCT for these disorders. Methods: Seven CALD, 2 MLD and 2 MPS-IH patients underwent HSCT between 2007 and 2014. Neurological examinations, magnetic resonance imaging, molecular and biochemical studies were obtained at baseline and repeated when appropriated. Results: Favorable outcomes were obtained with 4/5 related and 3/6 unrelated donors. Two patients died from procedure-related complications. Nine transplanted patients were alive after a median of 3.7 years: neurological stabilization was obtained in 5/6 CALD, 1/2 MLD, and one MPS-IH patient. Brain lesions of the MPS-IH patient were reduced four years after HSCT. Conclusion: Good outcomes were obtained when HSCT was performed before adulthood, early in the clinical course, and/or from a related donor.

@article{
 title = {Bioinformatics, interaction network analysis, and neural networks to characterize gene expression of radicular cyst and periapical granuloma},
 type = {article},
 year = {2015},
 keywords = {Endodontics,TH1,TH2,gene,high throughput biology},
 pages = {877-883},
 volume = {41},
 id = {95d72dad-eb61-3c04-b7c0-bacbe9411432},
 created = {2018-01-16T17:29:07.985Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:04.973Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Introduction Bioinformatics has emerged as an important tool to analyze the large amount of data generated by research in different diseases. In this study, gene expression for radicular cysts (RCs) and periapical granulomas (PGs) was characterized based on a leader gene approach. Methods A validated bioinformatics algorithm was applied to identify leader genes for RCs and PGs. Genes related to RCs and PGs were first identified in PubMed, GenBank, GeneAtlas, and GeneCards databases. The Web-available STRING software (The European Molecular Biology Laboratory [EMBL], Heidelberg, Baden-Württemberg, Germany) was used in order to build the interaction map among the identified genes by a significance score named weighted number of links. Based on the weighted number of links, genes were clustered using k-means. The genes in the highest cluster were considered leader genes. Multilayer perceptron neural network analysis was used as a complementary supplement for gene classification. Results For RCs, the suggested leader genes were TP53 and EP300, whereas PGs were associated with IL2RG, CCL2, CCL4, CCL5, CCR1, CCR3, and CCR5 genes. Conclusions Our data revealed different gene expression for RCs and PGs, suggesting that not only the inflammatory nature but also other biological processes might differentiate RCs and PGs.},
 bibtype = {article},
 author = {Poswar, Fabiano De Oliveira and Farias, Lucyana Conceição and Fraga, Carlos Alberto De Carvalho and Bambirra, Wilson and Brito-Júnior, Manoel and Sousa-Neto, Manoel Damião and Santos, Sérgio Henrique Souza and De Paula, Alfredo Maurício Batista and D'Angelo, Marcos Flávio Silveira Vasconcelos and Guimarães, André Luiz Sena},
 doi = {10.1016/j.joen.2015.02.004},
 journal = {Journal of Endodontics},
 number = {6}
}

Introduction Bioinformatics has emerged as an important tool to analyze the large amount of data generated by research in different diseases. In this study, gene expression for radicular cysts (RCs) and periapical granulomas (PGs) was characterized based on a leader gene approach. Methods A validated bioinformatics algorithm was applied to identify leader genes for RCs and PGs. Genes related to RCs and PGs were first identified in PubMed, GenBank, GeneAtlas, and GeneCards databases. The Web-available STRING software (The European Molecular Biology Laboratory [EMBL], Heidelberg, Baden-Württemberg, Germany) was used in order to build the interaction map among the identified genes by a significance score named weighted number of links. Based on the weighted number of links, genes were clustered using k-means. The genes in the highest cluster were considered leader genes. Multilayer perceptron neural network analysis was used as a complementary supplement for gene classification. Results For RCs, the suggested leader genes were TP53 and EP300, whereas PGs were associated with IL2RG, CCL2, CCL4, CCL5, CCR1, CCR3, and CCR5 genes. Conclusions Our data revealed different gene expression for RCs and PGs, suggesting that not only the inflammatory nature but also other biological processes might differentiate RCs and PGs.

@article{
 title = {Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma},
 type = {article},
 year = {2015},
 keywords = {Actinic keratosis,Basal cell carcinoma,Matrix metalloproteinase-2,Membrane-type matrix metalloproteinase-1,Squamous cell carcinoma},
 pages = {20-25},
 volume = {23},
 id = {63845991-be7a-3f75-9e2a-4d0bcbb1d361},
 created = {2018-01-16T17:29:08.084Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:16.059Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P <.05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC.},
 bibtype = {article},
 author = {Poswar, Fabiano De Oliveira and Fraga, Carlos Alberto De Carvalho and Gomes, Emisael Stênio Batista and Farias, Lucyana Conceic¸ão and Souza, Linton Wallis Figueiredo and Santos, Sérgio Henrique Souza and Gomez, Ricardo Santiago and Batista De-Paula, Alfredo Maurício and Guimarães, André Luiz Sena},
 doi = {10.1177/1066896914540998},
 journal = {International Journal of Surgical Pathology},
 number = {1}
}

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P <.05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC.

@article{
 title = {Elosulfase alfa decreases glycosaminoglycan storage in white blood cells from Morquio syndrome type A patients undergoing enzyme replacement},
 type = {article},
 year = {2015},
 pages = {S17-S18},
 volume = {114},
 websites = {https://linkinghub.elsevier.com/retrieve/pii/S1096719214004016},
 month = {2},
 id = {6935b4ae-69dc-36ee-8fa2-19eaae121c73},
 created = {2020-02-15T13:16:14.470Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:54.601Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Baldo, Guilherme and Poswar, Fabiano and Federhen, Andressa and Gus, Rejane and Bender, Fernanda and Giugliani, Roberto},
 doi = {10.1016/j.ymgme.2014.12.021},
 journal = {Molecular Genetics and Metabolism},
 number = {2}
}

@article{
 title = {Factors associated with unfavorable outcomes following mild pediatric head injuries in a reference center of the north region of Minas Gerais},
 type = {article},
 year = {2014},
 keywords = {Brain injuries,Child,Craniocerebral trauma},
 pages = {416-421},
 volume = {47},
 id = {f0390227-f0f0-3d1e-a87b-fec18911a5a7},
 created = {2018-01-16T17:29:07.705Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:13.849Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Study Design: Prospective cohort.Objective: To describe clinical and demographic characteristics of a sample of children with HI referred for acute care in a referral center of the north region of Minas Gerais, Brazil, and assess clinical and radiological markers associated with unfavorable outcomes.Methodology: All children between the ages 0 to 14 years referred with head injury from February to September 2011 were included in this study. Socio-demographic and clinical data were collected at the moment of the initial assessment under informed consent. The patients were also reassessed via telephone calls after 7 and 91 days. Results: A total of 77 patients were included in this study. The mean age was 3.9 years with a standard deviation of 3.76 years. Falls and bicycle collisions were the main mechanisms of trauma. The most relevant clinical marker associated with unfavorable outcomes at 7 days was the parental perception of unusual behavior (Odds Ratio = 11.33; 95% confidence interval: 1.38-93.13; p = 0.02). Computer tomography scan abnormalities were associated with both unfavorable outcomes at 7 days (p=0.03) and at 91 days (p=0.02).Conclusions: The peculiar aspects of head injuries in a Brazilian population were described in this study. It was also found that unusual behavior and abnormalities on CT scan are factors that predict unfavorable outcomes in children with mild HI in this population.},
 bibtype = {article},
 author = {Poswar, Fabiano O. and Gonçalves, Caroline R. and Rebouças, Bruno H. and De Souza, Samuel B.F. and Rodrigues, Lázaro Inácio A. and Neto, Paulino C.Fonseca and Diniz, Ana Júlia B. and Rocha, Júlia Thalita Q. and Barros, Laura O. and Santos, José Flávio C.},
 doi = {10.11606/issn.2176-7262.v47i4p:416-421},
 journal = {Medicina (Brazil)},
 number = {4}
}

Study Design: Prospective cohort.Objective: To describe clinical and demographic characteristics of a sample of children with HI referred for acute care in a referral center of the north region of Minas Gerais, Brazil, and assess clinical and radiological markers associated with unfavorable outcomes.Methodology: All children between the ages 0 to 14 years referred with head injury from February to September 2011 were included in this study. Socio-demographic and clinical data were collected at the moment of the initial assessment under informed consent. The patients were also reassessed via telephone calls after 7 and 91 days. Results: A total of 77 patients were included in this study. The mean age was 3.9 years with a standard deviation of 3.76 years. Falls and bicycle collisions were the main mechanisms of trauma. The most relevant clinical marker associated with unfavorable outcomes at 7 days was the parental perception of unusual behavior (Odds Ratio = 11.33; 95% confidence interval: 1.38-93.13; p = 0.02). Computer tomography scan abnormalities were associated with both unfavorable outcomes at 7 days (p=0.03) and at 91 days (p=0.02).Conclusions: The peculiar aspects of head injuries in a Brazilian population were described in this study. It was also found that unusual behavior and abnormalities on CT scan are factors that predict unfavorable outcomes in children with mild HI in this population.

@techreport{
 title = {Gorlin-Goltz syndrome: case report and review of literature},
 type = {techreport},
 year = {2014},
 source = {Clin. biomed. res},
 keywords = {Basal Cell Nevus Syndrome,Gorlin-Goltz Syndrome,Humans,Infant,Male,Musculoskeletal Abnormalities,Neoplasms,Newborn,Symptom Assessment,bifid rib,skin cancer},
 pages = {313-317},
 volume = {34},
 issue = {3},
 websites = {http://seer.ufrgs.br/hcpa},
 id = {237061f8-45e6-3cd8-b2f8-89118e399643},
 created = {2020-02-15T13:27:56.418Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:56.103Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Description of a case report of Gorlin-Goltz Syndrome diagnosed in a male newborn who presented increased head circumference and bifid ribs. Mother and grandmother presented typical physical findings of the syndrome, including palmar pits, odontogenic cysts, and history of multiple skin cancer resections. The diagnosis was based on clinical findings of three relatives. A literature review is also presented.},
 bibtype = {techreport},
 author = {Rahde Bischoff, Adrianne and Mercedes Timana Delgado, Yina and de Oliveira Poswar, Fabiano and Tarasconi Ruschel, Eduardo and Kohls Toralles, Eduardo and Lona Curubeto Lona de Miranda, Gabriel and Francisco Silveira Rita, Mario and Alegre, Porto}
}

Description of a case report of Gorlin-Goltz Syndrome diagnosed in a male newborn who presented increased head circumference and bifid ribs. Mother and grandmother presented typical physical findings of the syndrome, including palmar pits, odontogenic cysts, and history of multiple skin cancer resections. The diagnosis was based on clinical findings of three relatives. A literature review is also presented.

@article{
 title = {Choque séptico em paciente com histoplasmose disseminada associada à AIDS: Relato de caso},
 type = {article},
 year = {2013},
 keywords = {Acquired immune deficiency syndrome,Histoplasmosis,Mycoses},
 pages = {283-286},
 volume = {55},
 id = {b0471fca-2259-3b55-9a86-62eff677facf},
 created = {2018-01-16T17:29:07.165Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:16.897Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {2fde94ea-60c9-4695-8b22-7e026d01c478,912acba1-9ccd-4ebd-9e82-02f2ca91f7e1},
 private_publication = {false},
 abstract = {Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, which may present itself as a serious infection in immunocompromised individuals. We present a case of 31-year-old female with newly diagnosed HIV infection and history of fever, general and respiratory symptoms and diffuse hyperchromic papules through the body. She was admitted, with rapid progression to septic shock, and the presence of neutrophils filled with yeast-like organisms was detected on peripheral blood smear hematoscopia on the third day of hospitalization. The following is a brief review on the clinical picture and management of histoplasmosis.},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Carneiro, Jair Almeida and Stuart, Janice Mendes and Feliciano, Jorge Patrick Oliveira and Nassau, Daniella Cristina},
 doi = {10.1590/S0036-46652013000400010},
 journal = {Revista do Instituto de Medicina Tropical de Sao Paulo},
 number = {4}
}

Histoplasmosis is a systemic mycosis caused by Histoplasma capsulatum, which may present itself as a serious infection in immunocompromised individuals. We present a case of 31-year-old female with newly diagnosed HIV infection and history of fever, general and respiratory symptoms and diffuse hyperchromic papules through the body. She was admitted, with rapid progression to septic shock, and the presence of neutrophils filled with yeast-like organisms was detected on peripheral blood smear hematoscopia on the third day of hospitalization. The following is a brief review on the clinical picture and management of histoplasmosis.

@article{
 title = {Immunohistochemical analysis of TIMP-3 and MMP-9 in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma},
 type = {article},
 year = {2013},
 keywords = {Actinic keratosis,Basal cell carcinoma,Matrix metalloproteinase-9,Squamous cell carcinoma,Tissue inhibitor of metalloproteinase 3},
 pages = {705-709},
 volume = {209},
 id = {3087b477-4336-3736-a567-158e2ad9d7c3},
 created = {2018-01-16T17:29:07.566Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:16.166Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 folder_uuids = {2fde94ea-60c9-4695-8b22-7e026d01c478,912acba1-9ccd-4ebd-9e82-02f2ca91f7e1},
 private_publication = {false},
 abstract = {The expression of metalloproteinases and their inhibitors has been related to different invasive and metastatic potentials in cancer. This study aims to investigate the immunohistochemical expression of TIMP-3 and MMP-9 in samples of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC), and actinic keratosis (AK). Immunohistochemistry was performed to evaluate the expression of TIMP-3 and MMP-9 in samples of BCC (n=22), SCC (n=10), and AK (n=15). Ten fields of both tumor parenchyma and tumor stroma were photographed and counted in image software. The ratio of positive cells to total cells was used to quantify the staining. A higher expression of MMP-9 was found in tumor stroma of SCC compared to BCC and AK. No significant differences in TIMP-3 expression were observed among the groups. Considering the well-described differences between these neoplasms, these results provide additional evidence of the role of MMP-9 in tumor invasiveness of keratinocyte-derived tumors. © 2013 Elsevier GmbH.},
 bibtype = {article},
 author = {Poswar, Fabiano O. and Fraga, Carlos A.C. and Farias, Lucyana C. and Feltenberger, John D. and Cruz, Vitória P.D. and Santos, Sérgio H.S. and Silveira, Christine M. and de Paula, Alfredo M.B. and Guimarães, André L.S.},
 doi = {10.1016/j.prp.2013.08.002},
 journal = {Pathology Research and Practice},
 number = {11}
}

The expression of metalloproteinases and their inhibitors has been related to different invasive and metastatic potentials in cancer. This study aims to investigate the immunohistochemical expression of TIMP-3 and MMP-9 in samples of basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SCC), and actinic keratosis (AK). Immunohistochemistry was performed to evaluate the expression of TIMP-3 and MMP-9 in samples of BCC (n=22), SCC (n=10), and AK (n=15). Ten fields of both tumor parenchyma and tumor stroma were photographed and counted in image software. The ratio of positive cells to total cells was used to quantify the staining. A higher expression of MMP-9 was found in tumor stroma of SCC compared to BCC and AK. No significant differences in TIMP-3 expression were observed among the groups. Considering the well-described differences between these neoplasms, these results provide additional evidence of the role of MMP-9 in tumor invasiveness of keratinocyte-derived tumors. © 2013 Elsevier GmbH.

@article{
 title = {Actinomicose comprometendo a medula espinhal: Um relato de caso},
 type = {article},
 year = {2012},
 keywords = {Actinomycosis,Chest wall,Lung},
 pages = {535-537},
 volume = {45},
 id = {9b491438-c93c-33ef-89ac-0fb91dc37e4f},
 created = {2018-01-16T17:29:07.062Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:05.105Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Actinomycosis is a rare, chronic, suppurative, granulomatous infection caused by a group of gram-positive anaerobic bacteria belonging to the natural flora of the oral cavity and gastrointestinal and urogenital tracts. It may involve several organs. This case study refers to pulmonary actinomycosis with chest wall involvement and cord compression in a 29-year-old male who presented with fever, cough, hemoptysis, neck pain, and paresis and plegia of the lower limbs of 5-month duration.},
 bibtype = {article},
 author = {Ramos, Maria Isabela Alves and Carneiro, Jair Almeida and Poswar, Fabiano de Oliveira and Nassau, Daniella Cristina and Colares, Fernando Antônio},
 doi = {10.1590/S0037-86822012000400026},
 journal = {Revista da Sociedade Brasileira de Medicina Tropical},
 number = {4}
}

Actinomycosis is a rare, chronic, suppurative, granulomatous infection caused by a group of gram-positive anaerobic bacteria belonging to the natural flora of the oral cavity and gastrointestinal and urogenital tracts. It may involve several organs. This case study refers to pulmonary actinomycosis with chest wall involvement and cord compression in a 29-year-old male who presented with fever, cough, hemoptysis, neck pain, and paresis and plegia of the lower limbs of 5-month duration.

@article{
 title = {Analysis of socio-demographic and systemic health factors and the normative conditions of oral health care in a population of the Brazilian elderly},
 type = {article},
 year = {2012},
 keywords = {dental caries,elderly,oral health,oral pathology,periodontal disease,tooth loss},
 volume = {29},
 id = {d1feaed4-50dc-3433-a762-804071b0ba84},
 created = {2018-01-16T17:29:07.302Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:32:16.763Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {Objective: To investigate the association of socio-demographic and systemic health factors according to the normative conditions of oral health care (dental caries, edentulism, periodontal disease and oral mucosal lesion) in elderly individuals. Material and methods: A cross-sectional study was carried out in a group of elderly with access to community health care (n = 200). The normative conditions of oral health were then investigated according to the WHO and the SB Brazil criteria. Bivariate analyses were evaluated by the chi-square test and Fisher's exact test. An estimation of prevalence for the covariates was performed using Poisson's regression models. Results: The prevalence of edentulism and oral mucosal lesions was detected in 58% and 21.5% of elderly patients, respectively. In the dentate subjects, the prevalence of dental caries and periodontal disease was 51.2% and 20.8%, respectively. Older men and individuals from lower-income groups exhibited a higher prevalence of dental caries. Elderly women, illiterate individuals, and individuals over the age of 65 years exhibited a higher prevalence of edentulism. Elderly 60-64 years old and those who are employed had a significant association with periodontal disease. Conclusion: Socio-demographic factors were associated with some notable oral diseases in the elderly. © 2010 The Gerodontology Society and John Wiley & Sons A/S.},
 bibtype = {article},
 author = {Mendes, Danilo Cangussu and De Oliveira Poswar, Fabiano and De Oliveira, Marcus Vinícius Mac Edo and Haikal, Desirée Sant Ana and Da Silveira, Marise Fagundes and De Barros Lima Martins, Andréa Maria Eleutério and De Paula, Alfredo Maurício Batista},
 doi = {10.1111/j.1741-2358.2010.00446.x},
 journal = {Gerodontology},
 number = {2}
}

Objective: To investigate the association of socio-demographic and systemic health factors according to the normative conditions of oral health care (dental caries, edentulism, periodontal disease and oral mucosal lesion) in elderly individuals. Material and methods: A cross-sectional study was carried out in a group of elderly with access to community health care (n = 200). The normative conditions of oral health were then investigated according to the WHO and the SB Brazil criteria. Bivariate analyses were evaluated by the chi-square test and Fisher's exact test. An estimation of prevalence for the covariates was performed using Poisson's regression models. Results: The prevalence of edentulism and oral mucosal lesions was detected in 58% and 21.5% of elderly patients, respectively. In the dentate subjects, the prevalence of dental caries and periodontal disease was 51.2% and 20.8%, respectively. Older men and individuals from lower-income groups exhibited a higher prevalence of dental caries. Elderly women, illiterate individuals, and individuals over the age of 65 years exhibited a higher prevalence of edentulism. Elderly 60-64 years old and those who are employed had a significant association with periodontal disease. Conclusion: Socio-demographic factors were associated with some notable oral diseases in the elderly. © 2010 The Gerodontology Society and John Wiley & Sons A/S.

@article{
 title = {Consanguinidade e síndrome de Wolfram: relato de caso},
 type = {article},
 year = {2012},
 keywords = {Adolescent,Consanguinity,Diabetes Mellitus,Humans,Male,Optic Atrophy,Wolfram Syndrome},
 pages = {155-7},
 volume = {10},
 websites = {http://files.bvs.br/upload/S/1679-1010/2012/v10n2/a2779.pdf},
 id = {2a8f29a9-d45c-397a-a6a2-7e3a19f2f207},
 created = {2020-02-15T13:29:57.613Z},
 file_attached = {true},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:57.338Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 abstract = {JUSTIFICATIVA E OBJETIVOS: A síndrome de Wolfram (SW) é uma condição neurodegenerativa rara, progressiva e de herança autossômica recessiva, envolvendo o sistema nervoso central, nervos periféricos e tecidos neuroendócrinos. Este estudo teve por objetivo relatar um caso de SW. RELATO DO CASO: Paciente do sexo masculino, 17 anos, admitido com quadro de retenção urinária, parestesias e fortes dores nos membros inferiores. Era portador de diabetes mellitus (DM) tipo 1 mal controlado negativo para anticorpos anti-GAD e anti-insulina e apresentava história familiar de consanguinidade, além de dois irmãos com DM. Durante sua avaliação, constataram-se presença de amaurose com atrofia óptica, redução da acuidade auditiva, baixa estatura, atraso puberal, distúrbios psiquiátricos e diabetes insipidus. Foi tratado de infecção urinária, porém apresentou piora súbita aos 35 dias de internação com quadro de crises convulsivas, hipotensão, insuficiência respiratória e óbito. CONCLUSÃO: O diagnóstico de SW deve ser considerado em pacientes com DM associado à atrofia do nervo óptico. BACKGROUND AND OBJECTIVES: Wolfram syndrome (WS) is a rare, progressive, autosomal recessive neurodegenerative disorder, involving the central nervous system, peripheral nerves and neuroendocrine tissues. This study aimed to reporta case of WS. CASE REPORT: A male patient, aged 17, was admitted with signs of urinary retention, paresthesias and severe pain in the lower limbs. He also had poorly controlled type 1 diabetes mellitus (DM) negative for anti-GAD and anti-insulin and had a family history of consanguinity, and two brothers with DM. During his assessment, he was found to have amaurosis with optic atrophy, decreased hearing acuity, short stature, delayed puberty, psychiatric disorders and diabetes insipidus. He was treated for urinary infection, but suddenly worsened at 35 days of hospital admission, with seizures, hypotension, respiratory failure and death. CONCLUSION: The diagnosis of WS should be considered in patients with DM associated with atrophy of the optic nerve.},
 bibtype = {article},
 author = {Poswar, Fabiano de Oliveira and Carneiro, Jair Almeida and Alves, Íngrid Mendes and Oliveira Júnior, Edmundo Rocha de and Dias, Levindo Tadeu Freitas de Figueiredo and Novais Neto, Ezequiel},
 journal = {Rev. Soc. Bras. Clín. Méd},
 number = {2}
}

JUSTIFICATIVA E OBJETIVOS: A síndrome de Wolfram (SW) é uma condição neurodegenerativa rara, progressiva e de herança autossômica recessiva, envolvendo o sistema nervoso central, nervos periféricos e tecidos neuroendócrinos. Este estudo teve por objetivo relatar um caso de SW. RELATO DO CASO: Paciente do sexo masculino, 17 anos, admitido com quadro de retenção urinária, parestesias e fortes dores nos membros inferiores. Era portador de diabetes mellitus (DM) tipo 1 mal controlado negativo para anticorpos anti-GAD e anti-insulina e apresentava história familiar de consanguinidade, além de dois irmãos com DM. Durante sua avaliação, constataram-se presença de amaurose com atrofia óptica, redução da acuidade auditiva, baixa estatura, atraso puberal, distúrbios psiquiátricos e diabetes insipidus. Foi tratado de infecção urinária, porém apresentou piora súbita aos 35 dias de internação com quadro de crises convulsivas, hipotensão, insuficiência respiratória e óbito. CONCLUSÃO: O diagnóstico de SW deve ser considerado em pacientes com DM associado à atrofia do nervo óptico. BACKGROUND AND OBJECTIVES: Wolfram syndrome (WS) is a rare, progressive, autosomal recessive neurodegenerative disorder, involving the central nervous system, peripheral nerves and neuroendocrine tissues. This study aimed to reporta case of WS. CASE REPORT: A male patient, aged 17, was admitted with signs of urinary retention, paresthesias and severe pain in the lower limbs. He also had poorly controlled type 1 diabetes mellitus (DM) negative for anti-GAD and anti-insulin and had a family history of consanguinity, and two brothers with DM. During his assessment, he was found to have amaurosis with optic atrophy, decreased hearing acuity, short stature, delayed puberty, psychiatric disorders and diabetes insipidus. He was treated for urinary infection, but suddenly worsened at 35 days of hospital admission, with seizures, hypotension, respiratory failure and death. CONCLUSION: The diagnosis of WS should be considered in patients with DM associated with atrophy of the optic nerve.

@article{
 title = {Agranulocitose induzida por dapsona em paciente com hanseníase: relato de caso},
 type = {article},
 year = {2011},
 keywords = {Agranulocytosis,Amoxicillin-Potassium Clavulanate Combination,Antibiotic Prophylaxis,Dapsone,Leprosy,Middle Aged,Tonsillitis},
 id = {6cd989fb-2d65-3718-8dc9-428897063ea8},
 created = {2018-08-14T04:28:29.082Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2021-10-19T17:30:56.673Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {true},
 hidden = {false},
 private_publication = {false},
 bibtype = {article},
 author = {Carneiro, Jair Almeida and Poswar, Fabiano de Oliveira and Ramos, Maria Isabela Alves and Nassau, Daniella Cristina and Veloso, Gianne Donato Costa},
 journal = {Rev. Soc. Bras. Clín. Méd}
}

@article{
 title = {Hyperplastic polyposis: Case report},
 type = {article},
 year = {2010},
 keywords = {Colorectal neoplasm,Colorectal surgery,Hyperplasia,Intestinal polyps},
 volume = {30},
 id = {76a9cb06-3fae-3a29-b504-50ac991d12a9},
 created = {2018-01-16T17:29:06.962Z},
 file_attached = {false},
 profile_id = {a1b2ded6-b257-3e56-ac7c-9d438762d170},
 last_modified = {2018-01-16T17:29:06.962Z},
 read = {false},
 starred = {false},
 authored = {true},
 confirmed = {false},
 hidden = {false},
 private_publication = {false},
 abstract = {Hyperplastic polyposis is a rare condition, characterized by the presence of multiple hiperplastic polyps in the colon. It is reported a case of a 29-year-old patient who presented hyperplastic polyposis associated with mixed polyps.},
 bibtype = {article},
 author = {Poswar, F.O. and Carneiro, J.A. and Monteiro, V.A. and de Freitas, M.O.S.},
 journal = {Revista Brasileira de Coloproctologia},
 number = {3}
}

Hyperplastic polyposis is a rare condition, characterized by the presence of multiple hiperplastic polyps in the colon. It is reported a case of a 29-year-old patient who presented hyperplastic polyposis associated with mixed polyps.