Allogeneic hematopoietic stem cell transplantation modulates neurodevelopmental trajectories in mucopolysaccharidosis: a longitudinal study of subtype-specific outcomes and age-dependent efficacy

Background Mucopolysaccharidosis (MPS) involves neurodevelopmental decline due to lysosomal dysfunction. Hematopoietic stem cell transplantation (HSCT) may modify disease progression, but subtype-specific outcomes remain unclear. Methods Fifty-seven MPS patients (aged 1–8 years) undergoing HSCT in Shanghai (2019–2024) were assessed longitudinally using Griffiths Mental Development Scales-Chinese (GDS-C) pre-HSCT and at 3, 12, and 24 months post-HSCT. Linear mixed models evaluated timepoint, age, and subtype effects. Results HSCT significantly improved locomotor function ( F = 111.57, p < 0.001), with greatest gains in MPS III (β = 59.57) and age-dependent decline (β = − 2.46/year). Personal-social function improved modestly ( F = 4.44, p = 0.039), while language/eye-hand coordination showed progressive gains ( p ≤ 0.001). Subtype influenced language ( F = 3.75) and coordination ( F = 2.89), with attenuated responses in MPS II. No Timepoint × Subtype interactions suggested uniform temporal effects. Conclusions HSCT stabilizes/improves neurodevelopment in MPS, modulated by subtype and transplant age. Early intervention optimizes outcomes, particularly for MPS III. Culturally adapted GDS-C enables precise monitoring, guiding HSCT timing and rehabilitation.