Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network

Genetics and Molecular Biology

Dafne Dain Gandelman Horovitz¹  Erlane Marques Ribeiro²  Louise Lapagesse de Camargo Pinto³  Ana Carolina de Paula⁴  Eugênia Ribeiro Valadares⁵  João Ivanildo da Costa Neri⁶  Ruy Pires de Oliveira Sobrinho⁷  Carlos Eduardo Steiner⁷  Luiz Roberto Silva⁸  Isabela Goulart⁸  Isabel C. Neves de Souza⁹  Luiz Carlos Santana-da-Silva⁹  Roberto Giuglianiand^1,10  Alícia Dorneles Dornelles^1,10  Ida Vanessa Doederlein Schwartz^1,10  Márcia Ribeiro^1,11  Charles Marques Lourenço^1,12  Chong Ae Kim^1,12 

[1] Fundação Oswaldo Cruz;Hospital Infantil Albert Sabin;Hospital Infantil Joana de Gusmão;Hospital Municipal da Criança e Adolescente;Hospital das Clínicas;Prefeitura de Parnamirim;Universidade Estadual de Campinas;Universidade Federal de Uberlândia;Universidade Federal do Pará;Universidade Federal do Rio Grande do Sul;Universidade Federal do Rio de Janeiro;Universidade de São Paulo;

关键词: enzyme replacement therapy;    Laronidase;    Mucopolysaccharidosis Type I;    alph-L-iduronidase;   

DOI  :  10.1590/S1415-47572014000100006

来源: DOAJ

【 摘 要 】

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alph-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ;±20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

【 授权许可】

Unknown