Mucopolysaccharidoses in northern Brazil : targeted mutation screening and urinary glicosaminoglycan excretion in patients undergoing enzyme replacement therapy

Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patient...

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Detalles Bibliográficos
Autores: Viana, Gustavo Monteiro, Lima, Nathalia Oliveira de, Cavaleiro, Rosely Maria dos Santos, Alves, Erik Artur Cortinhas, Souza, Isabel Cristina Neves de, Feio, Raimunda Helena Ferreira, Leistner-Segal, Sandra, Schwartz, Ida Vanessa Doederlein, Giugliani, Roberto, Silva, Luiz Carlos Santana da
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:Brasil
Institución:Universidade Federal do Rio Grande do Sul (UFRGS)
Repositorio:Repositório Institucional da UFRGS
Idioma:inglés
OAI Identifier:oai:www.lume.ufrgs.br:10183/189561
Acceso en línea:http://hdl.handle.net/10183/189561
Access Level:acceso abierto
Palabra clave:Mucopolissacaridoses
Terapia de reposição de enzimas
Glicosaminoglicanos
Mucopolysaccharidosis
Glycosaminoglycans
Mutations
Enzyme replacement therapy
Descripción
Sumario:Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.

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