Wolman Disease / Cholesteryl Ester Storage Disease (LIPA)
Lysosomal acid lipase deficiency consists of two disorders known as Wolman disease and cholesterol ester storage disease. Both diseases are caused by pathogenic variants in the gene LIPA and are inherited in an autosomal recessive manner. While reported in multiple ethnicities, is it most prevalent in Sephardic Jewish individuals from Iran due to the presence of a founder mutation. Cholesterol ester storage disease is the more common form. In this disease, blood cells known as macrophages become filled with cholesteryl esters, which causes increased levels of cholesterol in the blood and progressive liver disease. Buildup of cholesterol in the arteries may also occur. This disease can present early and lead to death in childhood or adolescence due to cirrhosis of the liver, or it may have a late onset with survival into adulthood. Wolman disease begins in infancy and has a more severe phenotype than cholesterol ester storage disease. Death occurs in infancy due to multi-organ failure caused by cholesterol infiltration and buildup. Pathogenic LIPA variants that result in a protein with some residual function are more likely to result in cholesterol ester storage disease rather than Wolman disease. Depending on the specific variants identified, it may be possible to predict whether a patient will develop Wolman disease or cholesterol ester storage disease.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.