Mucopolysaccharidoses in northern Brazil: Targeted mutation screening and urinary glycosaminoglycan excretion in patients undergoing enzyme replacement therapy

Abstract

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.

Application of pathogenicity scores as diagnostic and prognostic markers for MPS disorders: In-silico analysis in MPS I

“…The reduction of GAG was of about 69% to 93%. This is in agreement with previous studies (Viana et al, 2011;Wraith et al, 2004;Wraith et al, 2007). One MPS patient had high GAG despite good clinical prognosis.…”

Utility of pathogenicity scores as diagnostic and prognostic markers for MPS disorders: In-silico analysis in MPS I

“…This is in agreement with previous studies. 44,45,46 One MPS patient had high GAG despite good clinical prognosis. An earlier study also showed high GAG even after 6-year of ERT.…”

Avaliação do consumo alimentar de pacientes com mucopolissacaridose

“…5 A Rede MPS Brasil, uma iniciativa criada para melhorar o diagnóstico e gestão destas doenças no Brasil, identificou, entre 2004 e 2006, 161 pacientes com MPS, entre os quais o tipo II mostrou maior prevalência (n=82) e o tipo VII o menor número de casos (n=4). 19 Estudos sugerem que as MPSs tipo II e VI sejam as mais frequentemente diagnosticadas no país, sendo desconhecidas as explicações para tal achado, e observada maior frequência no Sudeste seguida da região Nordeste. 1,2 No estudo de Villas-Boas et al, 20 de 2011, realizado no mesmo centro de referência do presente estudo, de 29 pacientes avaliados, 11 (38%) tinham diagnóstico de MPS tipo II, e o sexo masculino foi o mais prevalente, perfazendo 82,8% do grupo total.…”