ESPE Abstracts

Background: Mucopolysaccharidosis I Hurler (MPS-IH is an inborn error of metabolism arising from the defective activity of alpha-L-iduronidase, an enzyme involved in the degradation of glycosaminoglycans (GAGs). As a result, the pathological lysosomal storage of GAGs in several tissues leads to multi-systemic complications, such as hepatosplenomegaly, progressive central nervous system deterioration, skeletal dysplasia and faltering growth, commonly resulting in overt short stature. Though hematopoietic stem cell transplantation (HSCT) represents the standard-of-care for MPS-IH patients < 2 years, its impact on growth has been historically regarded as unsatisfactory. Nevertheless, the growth patterns recorded in transplanted patients have always been compared to those of healthy children.

Aims: We aimed at verifying the impact of HSCT on MPS-IH long term growth achievements by comparing the patterns of transplanted children with those of not transplanted ones.

Materials and methods: Fifteen transplanted patients (4 males, 26.7%) aged 15.6 ± 5.4 years at the time of data collection and diagnosed with MPS-IH at a mean age of 11.4 ± 4.3 months (range: 4.9 – 18.1) were included in the study population. All these patients had been reviewed from a clinical and auxological perspective 3- to 6-monthly after transplantation for the first 5 years and annually thereafter. The auxological data of all the patients were assessed longitudinally and compared both to the WHO growth centiles for healthy children and to the curves for not transplanted MPS-IH children published in 2020. We retrospectively processed the auxological data measured 6 months before HSCT (t_-6), at the time of HSCT (t_o) and subsequently 12-monthly for the first 5 years after transplantation (t₁₂, t₂₄, t₃₆, t₄₈, t₆₀), at the age of 9 years (t_9yrs) and at final height.

Results: Despite a progressive decrease after HSCT with reference to the WHO growth charts, median height SDS showed a progressive and statistically significant increase when comparing the stature recorded at each timepoint with the curves of not transplanted MPS-IH (from -0.39 SDS at t0 to +1.35 SDS 5 years after HSCT, P <0.001). Median height SDS was statistically higher than t₀ from t₂₄ onwards, with statistical significance progressively increasing in time. Upon t_9yrs, height SDS was + 3.67, statistically higher than t₀ P <0.0001.

Conclusions: Though not efficient enough to restore a normal growth pattern in MPS-IH patients, we hereby demonstrate that HSCT positively affects growth and provides transplanted patients with a remarkable height gain compared to untreated gender- and age- matched individuals.