Ten-year enzyme replacement therapy in early childhood-onset lysosomal acid lipase deficiency: A case report

Abstract

BACKGROUND

Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lipid storage disorder caused by biallelic pathogenic variants in the LIPA gene. The clinical phenotype ranges from the rapidly progressive infantile form (Wolman disease), which usually results in death within the first year of life, to the childhood/adult-onset form, historically known as cholesteryl ester storage disease. Diagnosis of the later-onset form is often delayed owing to nonspecific clinical features, such as hepatomegaly, elevated transaminases, dyslipidemia resembling heterozygous familial hypercholesterolemia, and/or intestinal manifestations such as malabsorption.

CASE SUMMARY

A 21-month-old boy presented with abdominal swelling and fever. Physical examination and laboratory evaluation revealed short stature, hepatomegaly, dyslipidemia, and mildly elevated hepatic enzyme levels. Liver biopsy showed fibrosis, lobular inflammation, microvesicular steatosis, and portal inflammation. Lysosomal acid lipase enzyme activity was undetectable, and genetic analysis revealed a biallelic c.894G>A (p.Gln298=) pathogenic variant in the LIPA gene, confirming the diagnosis of LAL-D. The patient was initiated on enzyme replacement therapy with sebelipase alfa at 3 years and 11 months of age through a compassionate use access program. Over 10 years of follow-up, the patient showed clear clinical benefit, including normalization of liver enzymes, improvements in dyslipidemia, reduction in hepatomegaly and hepatic fat content, improvement in liver histopathology, and catch-up growth. No treatment-related adverse effects were observed.

CONCLUSION

This case highlights the long-term effectiveness and safety of sebelipase alfa initiated in early childhood and emphasizes the importance of early recognition and treatment of LAL-D to prevent irreversible organ damage and disease progression.

Keywords: Cholesteryl ester storage diseases; Wolman disease; Enzyme replacement treatment; Sebelipase alfa; Lysosomal acid lipase deficiency; Lysosomal storage disorders; Case report

Core Tip: Early diagnosis of lysosomal acid lipase deficiency (LAL-D) is challenging owing to its nonspecific clinical presentation. We report a rare case diagnosed before the age of 4 years, with long-term follow-up after early initiation of enzyme replacement therapy. Our patient showed marked improvements in growth, liver function, and histology over 10 years, with no treatment-related adverse events. This case highlights the importance of early recognition and timely treatment of LAL-D to optimize long-term outcomes in affected children.