2025/09/01 by Maurizio Scarpa, George A. Díaz, Roberto Giugliani +8 · 1 voice
Medicine · #Lysosomal Storage Disorders Research #Biomedical Research and Pathophysiology #Glycogen Storage Diseases and Myoclonus
paper · pdf · doi:10.1002/jimd.70086
openalex publication_date 2025/09/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
ABSTRACT Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease characterized by hepatosplenomegaly, pulmonary dysfunction, dyslipidemia, and growth deficits. Olipudase alfa (recombinant‐human ASM) is the only treatment for non‐central‐nervous‐system ASMD manifestations in children and adults. An open‐label long‐term study followed 4 to 8 years of olipudase alfa treatment in 20 children and adolescents with ASMD (baseline age (years) 1.5–17.5). At final assessments, splenomegaly and hepatomegaly were reduced relative to baseline (mean percent decrease in spleen and liver volumes 78% ± 1.2% and 59.8% ± 1.5%, respectively). Baseline splenomegaly was severe (spleen volume > 15 MN [multiples of normal]) or moderate (5–15 MN) ( n = 12 and n = 8, respectively) versus mild/absent (< 5 MN) ( n = 12) or moderate ( n = 8) at final assessment. Baseline hepatomegaly was severe (liver volume > 2.5 MN) ( n = 10) or moderate (1.25–2.5 MN) ( n = 10) versus mild/absent (< 1.25 MN) ( n = 19) or moderate ( n = 1) at final assessment. Among nine individuals able to perform assessments, diffusing capacity of the lung for carbon monoxide (DL CO ) impairment was severe (< 40%) ( n = 1), moderate (40%–60%) ( n = 4), or mild (60%–80%) ( n = 4) at baseline versus absent ( n = 4), mild ( n = 4) or moderate ( n = 1) at final assessment. Mean percent increase in DL CO was 53.7% ± 6.5%. At baseline, 10/20 children had clinical short stature (height Z ‐scores ≤ − 2) at baseline versus 0/20 at the final assessment. Atherogenic lipid profiles and liver function tests normalized within 2 years and remained stable. Adverse events were mostly mild or moderate, with 4 individuals experiencing 7 serious adverse events, all recovered/resolved. Interpretation: Enzyme replacement therapy with olipudase alfa in children and adolescents with chronic ASMD was well‐tolerated with clinically meaningful improvements in multiple disease parameters. Trial Registration: NCT02004704.