Wolman disease is a severe lysosomal storage disorder caused by a deficiency of the enzyme lysosomal acid lipase (LAL). This enzyme is responsible for breaking down cholesteryl esters and triglycerides into free cholesterol and fatty acids. The disorder results from mutations in the LIPA gene. When LAL is absent or severely reduced, fats accumulate rapidly in cells of the liver, spleen, adrenal glands, intestines, and bone marrow, leading to widespread organ dysfunction. Wolman disease represents the most severe end of the lysosomal acid lipase deficiency spectrum.

Symptoms usually appear within the first weeks or months of life and progress rapidly. Infants commonly develop: • Failure to thrive • Chronic diarrhea and vomiting • Poor absorption of nutrients • Severe weight loss Other features include: • Massive enlargement of the liver and spleen • Liver failure and jaundice • Calcification of the adrenal glands (a hallmark finding) • Anemia and thrombocytopenia • Progressive multi-organ failure Without treatment, most infants do not survive beyond the first year of life.

Wolman disease is caused by mutations in the LIPA gene.

Diagnosis is based on: • Clinical presentation • Enzyme assays showing absent or severely reduced LAL activity • Genetic testing • Imaging studies showing adrenal calcifications Early diagnosis is critical for treatment initiation.

Treatment options include: • Enzyme replacement therapy (sebelipase alfa) • Nutritional and supportive care • Management of liver disease and metabolic complications ERT has significantly improved survival and outcomes in affected infants.