Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: Analysis of eight sibling pairs

Sanofi Co, Genzyme, Cambridge, MA USAJohns Hopkins Aramco Healthcare, Dhahran, Saudi ArabiaUniv Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL 33136 USARobert Boulin Hosp, Serv Pediat, Libourne, FrancePellegrin Hosp, CHU Bordeaux, Genet Serv, Bordeaux, FranceChildrens Hosp Cordoba, Metab Sect, Cordoba, ArgentinaUniv Manchester, St Marys Hosp, Manchester Ctr Genom Med, CMFT, Manchester M13 0JH, Lancs, EnglandUniversidade Federal de São Paulo, Reference Ctr Inborn Errors Metab, São Paulo, BrazilBrown Univ, Dept Pediat, Div Human Genet, Hasbro Childrens Hosp, Providence, RI 02912 USAGen Hosp Segovia, Div Pediat, Segovia, SpainUniv Bordeaux, Bordeaux, FranceUniversidade Federal de São Paulo, Reference Ctr Inborn Errors Metab, São Paulo, BrazilWeb of Scienc

Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships

Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations. This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively. Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up. These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations