Deficient activity of lysosomal acid lipase results in massive accumulation of cholesteryl esters and triglycerides in most tissues of the body. Both of these lipids are substrates for the enzyme, one of the major functions of which is the hydrolysis of cholesteryl esters in various lipoproteins as they are removed from plasma by tissues in the periphery. The deficiency state is expressed in two major phenotypes: Wolman disease and cholesteryl ester storage disease.

Wolman disease occurs in infancy and is nearly always fatal before the age of 1 year. Hepatosplenomegaly, steatorrhea, abdominal distension, other gastrointestinal symptoms, adrenal calcification demonstrable on x-ray examination, and failure to thrive are observed in the first weeks of life.

Cholesteryl ester storage disease can be more benign. It may not be detected until adulthood. Lipid deposition is widespread, although hepatomegaly may be the only clinical abnormality. Hyperbetalipoproteinemia is common, and premature atherosclerosis may be severe. Adrenal calcification is rare.

Diagnosis of both disorders is based on the clinical picture combined with demonstration of acid lipase deficiency in cultured skin fibroblasts, lymphocytes, or other tissues. Both Wolman disease and cholesteryl ester storage disease are autosomal recessive disorders, involving the structural gene for acid lipase, which is located on chromosome 10q23.2-q23.3. Wolman disease is caused by a variety of different mutations, leading to complete elimination of the enzyme function. Conversely, one relatively common allele, associated with ∼5 percent residual activity, is responsible for most cases of cholesteryl ester storage disease.

There is no specific therapy, but the suppression of cholesterol synthesis and apolipoprotein B production by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in combination with cholestyramine treatment and a diet excluding foods rich in cholesterol and triglycerides results in a noticeable clinical improvement in at least some cases of cholesteryl ester storage disease. Prenatal diagnosis is based on the absence of acid lipase activity in cultured chorionic villus cells. In addition, genotyping of chorionic villus DNA can be used to confirm the diagnosis.