Effectiveness of early initiation of idursulfase in infants and very young children with mucopolysaccharidosis II: a retrospective chart review in siblings

Introduction: Enzyme replacement therapy (ERT) with intravenous idursulfase is the standard of care for patients with mucopolysaccharidosis II (MPS II; Hunter syndrome). Data are limited for children aged ≤12 months. This retrospective study evaluated outcomes with early ERT. Methods: Male siblings with MPS II treated with idursulfase for >2 years were categorized into five cohorts by age at treatment initiation. The primary objective compared Cohort 1 (ERT initiation aged ≤12 months) with Cohort 2 (ERT initiation at an age ≥ 12 months older). Clinical outcomes were compared using Kaplan–Meier and Cox proportional models, and generalized linear mixed models (GLMMs) for variables with adequate data. Results: Overall, 38 patients (19 sibling pairs) were included; the primary analysis included 15 per cohort. Median (10th–90th percentile) age at idursulfase initiation was 3.0 (1.0–11.0) and 44.0 (28.0–84.0) months and mean (standard deviation) follow-up was 69.7 (42.5) and 130.6 (46.8) months in Cohorts 1 and 2, respectively. First events from birth of abnormal liver size, joint stiffness, carpal tunnel syndrome, and enlarged tonsils and adenoids occurred less frequently in Cohort 1 than 2; first events of surgery or cardiac valve disease occurred more frequently in Cohort 1 than 2. GLMM analyses showed that, compared with their older siblings, patients who initiated ERT aged ≤12 months had better clinical outcomes for height-for-age Z -score, liver, cardiac, and musculoskeletal manifestations. Discussion: Early ERT may improve clinical outcomes in MPS II, supporting the known efficacy of idursulfase and adding to the limited evidence for early ERT.