Benefits of early intervention with olipudase alfa in symptomatic children with acid sphingomyelinase deficiency: A sibling case-comparison study

Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disease with multisystem complications including neurodegeneration, hepatosplenomegaly, interstitial lung disease (ILD), bone marrow disease, and growth failure. Non-neurological manifestations of this disease are amenable to enzyme replacement therapy (ERT) with olipudase alfa in both adult and pediatric patients. In this study, we offer evidence for the role of intervention in early childhood pediatric cases. We present longitudinal follow-up for two siblings with ASMD (<i>SMPD1</i> p.R498L/p.R610del compound heterozygous genotype) who were started on ERT at different ages (ages 3 and 7, duration of treatment >4 years). After initiation of ERT, both siblings demonstrated significant radiographic improvement of interstitial lung disease (ILD), organomegaly, and growth. Notably, the younger sibling who had started earlier on treatment did not experience any deceleration in growth parameters and has normal height and weight for age, while the older sibling showed a decline in growth velocity that improved once treatment was initiated. Similarly, the older sibling showed similar-to-worse ILD and more persistent organomegaly compared to the younger sibling. Treatment has resulted in sustained improvements in both patients. These findings suggest that early intervention with ERT in ASMD may have cumulative benefits for pediatric health and motivate early screening for ASMD in pediatric patients.