Survival, growth, and safety findings in patients with rapidly progressive, infantile-onset LAL-D: Results from the international LAL-D registry

Suresh Vijay ¹, Jennifer Evans ², Florence Lacaille ³

⁰University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Molecular Genetics and Metabolism +

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November 21, 2025

View abstract on PubMed

Summary

Enzyme replacement therapy with sebelipase alfa significantly improved survival rates in infants with rapidly progressive lysosomal acid lipase deficiency (LAL-D). Long-term outcomes show sustained benefits in growth and liver health for LAL-D patients.

Area Of Science

Biochemistry
Genetics
Pediatrics

Background

Lysosomal acid lipase deficiency (LAL-D), historically known as Wolman disease, is a severe genetic disorder.
Symptomatic infants typically experience rapid disease progression, including hepatosplenomegaly, liver failure, and failure to thrive, often leading to death within six months if untreated.
Sebelipase alfa is an enzyme replacement therapy (ERT) for LAL-D.

Purpose Of The Study

To evaluate the long-term outcomes of sebelipase alfa ERT in infants with rapidly progressive LAL-D.
To assess survival rates, growth, liver parameters, and safety in patients treated with sebelipase alfa.

Main Methods

Analysis of patient data from the International LAL-D Registry (NCT01633489), an ongoing observational, multicenter study.
Inclusion of 29 infants with rapidly progressive LAL-D treated with sebelipase alfa.
Data collection on patient demographics, ERT dosage, survival, growth (weight-for-age z scores), adverse events, and antidrug antibodies.

Main Results

Overall survival rate was 93% (27 of 29 patients) during a median observation period of 6.2 years.
Weight-for-age z scores improved or stabilized in 5 of 11 patients with baseline low scores.
Adverse events were reported in 79% of patients, with 38% experiencing events potentially related to sebelipase alfa, mostly mild and resolved. Antidrug antibodies were detected in some patients.

Conclusions

Sebelipase alfa ERT demonstrates a dramatic survival benefit for infants with symptomatic, rapidly progressive LAL-D.
The therapy offers significant metabolic and growth improvements, confirming its efficacy in managing this rare genetic disorder.
Long-term monitoring for adverse events and antidrug antibodies is important in patients receiving sebelipase alfa.

Keywords:

Enzyme replacement therapy Lysosomal acid lipase deficiency Registry Sebelipase alfa