Enzyme replacement therapy in cholesteryl ester storage disease: A case report on lysosomal acid lipase deficiency management.

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disorder caused by pathogenic variants in the LIPA gene. The clinical spectrum ranges from early-onset Wolman disease to later presentations in childhood and adulthood, formerly known as cholesteryl ester storage disease (CESD). Impaired lysosomal acid lipase (LAL) activity leads to the accumulation of cholesteryl esters and triglycerides, causing progressive hepatic and metabolic dysfunction.

Case presentation: We describe a 17-year-old Mexican female diagnosed with CESD at age 13 after evaluation for short stature and severe hypercholesterolemia. Laboratory workup revealed markedly elevated liver enzymes and lipid levels, with severely reduced LAL activity. Molecular testing identified a homozygous LIPA(NM_000235.3):c.894G>A variant. Enzyme replacement therapy (ERT) with sebelipase alfa (1 mg/kg biweekly) was initiated, leading to progressive normalization of lipid and hepatic profiles. Over a 48-month follow-up, the patient exhibited catch-up growth (gain of 17 cm and 21 kg), pubertal development with the onset of menarche at age 16, and achievement of Tanner stage III.

Conclusion: This case underscores the importance of early recognition of CESD in patients with unexplained dyslipidemia, elevated liver enzymes, and growth delay. Timely initiation of sebelipase alfa resulted in favorable biochemical and clinical outcomes. Comprehensive diagnostic evaluation-including enzymatic and genetic testing-is critical for accurate diagnosis and personalized management of LAL-D.