Lysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive genetic disorder. Biallelic pathogenic variants within the LIPA gene result in a deficiency of the lysosomal acid lipase (LAL) enzyme, which is crucial for the hydrolysis of cholesteryl esters (CE) via the endocytic pathway. This enzymatic defect consequently leads to the lysosomal accumulation of CE and triglycerides. The phenotype of LAL-D varies significantly depending on the specific genetic variation. Specifically, null allelic variants, characterized by the absence of residual enzymatic function, manifest as Wolman’s disease, while variants with some residual LAL enzymatic activity result in cholesterol ester storage disease (CESD). Notably, identifying individuals with LAL-D poses a significant challenge, given the phenotypic heterogeneity of the disease, which can potentially overlap with various differential diagnoses.

Wolman’s disease usually manifests in infancy. The clinical presentation includes vomiting, steatorrhea, and abdominal distension within the first few days of life. Hepatosplenomegaly may occur due to lipid deposition in the liver and spleen, and hepatic steatosis can lead to liver failure. The accumulation of CE and triglycerides in the gastrointestinal tract leads to intestinal wall thickening, which in turn causes malabsorption and subsequent malnutrition. Calcification of the adrenal glands is a classic feature of the disease and can lead to adrenal cortical insufficiency. Individuals with Wolman’s disease rarely survive beyond their first year of life, primarily due to severe malnutrition, liver failure, and adrenal cortical insufficiency. Although enzyme replacement therapy is considered, life expectancy remains limited due to the disease’s severity. Hematopoietic stem cell transplantation represents another therapeutic option; however, further studies are necessary due to conflicting findings reported in the literature.^,

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