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

TL;DR

This study shows that hematopoietic stem cell transplantation can improve neurodevelopment in mucopolysaccharidosis, with the best results in younger patients and specific subtypes.

Contribution

The study provides subtype-specific and age-dependent insights into HSCT efficacy for neurodevelopment in MPS patients.

Findings

HSCT significantly improves locomotor function, especially in MPS III patients.

Early HSCT (≤ 4 years) optimizes motor and language outcomes.

Culturally adapted GDS-C enables precise monitoring of Chinese MPS patients.

Abstract

Mucopolysaccharidosis (MPS) involves neurodevelopmental decline due to lysosomal dysfunction. Hematopoietic stem cell transplantation (HSCT) may modify disease progression, but subtype-specific outcomes remain unclear.

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.

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.

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.

HSCT stabilizes/improves neurodevelopment in MPS, with MPS III showing greatest gains.Early HSCT (≤ 4 years) optimizes motor and language outcomes.Culturally adapted GDS-C enables precise longitudinal monitoring in Chinese MPS patients.Subtype-specific responses highlight attenuated efficacy in MPS II language function.Age-dependent decline underscores irreversible CNS damage risks in delayed transplantation.

HSCT stabilizes/improves neurodevelopment in MPS, with MPS III showing greatest gains.

Early HSCT (≤ 4 years) optimizes motor and language outcomes.

Culturally adapted GDS-C enables precise longitudinal monitoring in Chinese MPS patients.

Subtype-specific responses highlight attenuated efficacy in MPS II language function.

Age-dependent decline underscores irreversible CNS damage risks in delayed transplantation.

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