Mucopolysaccharidosis VII in Brazil: natural history and clinical findings

Orphanet Journal of Rare Diseases

Carlos Henrique Paiva Grangeiro¹  Diego Santana Chaves Geraldo Miguel²  Liane de Rosso Giuliani³  Paula Frassinetti Vasconcelos de Medeiros⁴  Maria Espírito Santo Almeida Moreira⁵  José Francisco da Silva Franco⁶  Isabel Neves de Souza⁷  Luiz Roberto da Silva⁸  Chong Ae Kim⁹  Luiz Carlos Santana da Silva^1,10  Anneliese Lopes Barth^1,11  Dafne Dain Gandelman Horovitz^1,11  Roberto Giugliani^1,12  Emilia Katiane Embiruçu de Araújo Leão^1,13  Melissa Rossi Calvão Dumas^1,14  Helena Maria Guimarães Pimentel dos Santos^1,14  Daniel Garcia^1,15  Tatiele Nalin^1,15 

[1] Complexo Hospitalar, Federal University of Ceará, Fortaleza, CE, Brazil;Escola Bahiana de Medicina E Saúde Pública, Salvador, BA, Brazil;Faculty of Medicine, Federal University of Mato Grosso Do Sul and Hospital Universitário Maria Aparecida Pedrossian (HUMAP/UFMS), Campo Grande, MS, Brazil;Federal University of Campina Grande, Campina Grande, PB, Brazil;Hospital Infantil Lucidio Portella, Teresina, PI, Brazil;Hospital Infantil Sabará -SP and University of São Paulo/ IPEN, São Paulo, SP, Brazil;Hospital Universitário Bettina Ferro de Souza, Federal University of Pará, Belém, PA, Brazil;Hospital de Clínicas, Federal University of Uberlândia, Uberlândia, MG, Brazil;Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina University of São Paulo, São Paulo, SP, Brazil;Laboratory of Inborn Errors of Metabolism, Institute of Biological Sciences, Federal University of Pará, INAGEMP, Belém, PA, Brazil;Medical Genetics Department, National Institute of Women, Children, and Adolescent Health, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil;Medical Genetics Service, HCPA, Department of Genetics, UFRGS, INAGEMP and DR Brasil Research Group, HCPA, Rua Ramiro Barcelos 2350, 90035-903, Porto Alegre, RS, Brazil;Medical Genetics Service, Hospital Universitário Prof. Edgard Santos, Salvador, BA, Brazil;Rare Diseases Service - APAE Salvador, Salvador, BA, Brazil;Ultragenyx Brasil Farmacêutica Ltda, São Paulo, SP, Brazil;

关键词: Mucopolysaccharidosis type VII;    Sly disease;    Lysosomal storage disorder;    Glycosaminoglycans;    Beta-glucuronidase deficiency;   

DOI  :  10.1186/s13023-021-01870-w

来源: Springer

【 摘 要 】

BackgroundMucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme β-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum.MethodsWe conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the “MPS Brazil Network” who were known to be alive in 2020 in Brazil (N = 13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population.ResultsThe majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant.ConclusionsThis case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.

【 授权许可】

CC BY