Growth Patterns in MPS IVA and MPS IIIA: A Longitudinal Single-Center Study.

Background/

Objectives

Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterized by impaired glycosaminoglycan degradation, leading to multisystem involvement and progressive growth impairment. Longitudinal growth data in MPS IVA and MPS IIIA, including the association of ERT with growth outcomes, remain limited. This study aimed to characterize growth trajectories in MPS IVA and MPS IIIA and to assess the association of ERT with Elosulfase alfa on growth outcomes in MPS IVA patients.

Methods

We retrospectively analyzed growth data from 39 patients with MPS subtypes IIIA and IVA followed at a single center between 2004 and 2024. Height and weight standard deviation scores (SDS) were calculated relative to CDC growth references and modeled using linear mixed-effects models (LMM). In the MPS IVA subgroup, the effect of ERT with Elosulfase alfa was assessed using LMM and paired SDS comparisons.

Results

Growth impairment was evident across both subtypes with distinct trajectories. MPS IIIA patients showed significant height decline after age six with progressive weight loss in later childhood. MPS IVA patients exhibited persistently severe short stature and a tendency toward overweight with advancing age. Among the 16 MPS IVA patients treated with Elosulfase alfa who were included in the analysis, height SDS declined significantly during treatment (-0.127 SDS/year [95% CI: -0.194, -0.061], p < 0.001), and the rate of decline was not significantly affected by age at ERT initiation (interaction p = 0.53).

Conclusions

ERT with Elosulfase alfa did not prevent progressive height loss relative to population norms. The rate of height SDS decline was not significantly influenced by the timing of ERT initiation (interaction p = 0.53), and causal conclusions cannot be drawn from this observational data.