title: Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network.
abstract: Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-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.
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil .
authors.forename: Alícia Dorneles
authors.initials: AD
authors.lastname: Dornelles
authors.affiliation: Medical Genetics Service, Hospital Infantil Joana de Gusmão, Florianópolis, SC, Brazil .
authors.forename: Louise Lapagesse
authors.initials: LL
authors.lastname: de Camargo Pinto
authors.affiliation: Hospital Municipal da Criança e Adolescente, Guarulhos, SP, Brazil .
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Paula
authors.affiliation: Department of Medical Genetics, Universidade Estadual de Campinas, Campinas, SP, Brazil .
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Steiner
authors.affiliation: Hospital das Clínicas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil .
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.affiliation: Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil .
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.affiliation: Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil .
authors.forename: Dafne Dain Gandelman
authors.initials: DD
authors.lastname: Horovitz
authors.affiliation: Medical Genetics Service, Hospital Infantil Albert Sabin, Fortaleza, CE, Brazil .
authors.forename: Erlane Marques
authors.initials: EM
authors.lastname: Ribeiro
authors.affiliation: Ambulatório de Erros Inatos do Metabolismo, Hospital das Clínicas, UFMG, Belo Horizonte, MG, Brazil .
authors.forename: Eugênia Ribeiro
authors.initials: ER
authors.lastname: Valadares
authors.affiliation: Hospital de Clínicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil .
authors.forename: Isabela
authors.initials: I
authors.lastname: Goulart
authors.affiliation: Hospital Universitário Bettina Ferro de Souza, Universidade Federal do Pará, Belém, PA, Brazil .
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Neves de Souza
authors.affiliation: Outpatient Genetics Clinic, Prefeitura de Parnamirim, Parnamirim, RN, Brazil .
authors.forename: João Ivanildo
authors.initials: JI
authors.lastname: da Costa Neri
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil .
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Santana-da-Silva
authors.affiliation: Hospital de Clínicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil .
authors.forename: Luiz Roberto
authors.initials: LR
authors.lastname: Silva
authors.affiliation: Instituto de Puericultura e Pediatria Martagão Gesteira, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil .
authors.forename: Márcia
authors.initials: M
authors.lastname: Ribeiro
authors.affiliation: Department of Medical Genetics, Universidade Estadual de Campinas, Campinas, SP, Brazil .
authors.forename: Ruy Pires
authors.initials: RP
authors.lastname: de Oliveira Sobrinho
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil . ; Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil .
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil . ; Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil .
authors.forename: Ida Vanessa Doederlein
authors.initials: IV
authors.lastname: Schwartz
keywords: Laronidase; Mucopolysaccharidosis Type I; alpha-L-iduronidase; enzyme replacement therapy