Lysosomal Acid Lipase Deficiency

Lysosomal acid lipase deficiency is a metabolic lipid storage disease. Two rare conditions may result from this deficiency (likely representing two ends of a clinical spectrum):

• Wolman disease: The early-onset and most severe form of the disease where lipids accumulate throughout the body, mostly in the liver, within the first weeks of life. Symptoms include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, a yellowish color of the skin and the whites of the eyes (jaundice), vomiting, diarrhea, fatty stool (steatorrhea), and poor absorption of nutrients from food (malabsorption), as well as calcium deposits in adrenal glands, anemia, liver disease (cirrhosis), and developmental delay. Infants with this form of lysosomal acid lipase deficiency develop failure in multiple organs, and severe malnutrition.
• Cholesteryl ester storage disease: Less severe and starting later in life. Symptoms may include hepatosplenomegaly, liver disease (cirrhosis), and  malabsorption with diarrhea, vomiting, and steatorrhea.

Lysosomal acid lipase deficiency is caused by mutations in the LIPA gene, which provides instructions to produce the lysosomal acid lipase enzyme. When there is not enough of this enzyme, the body cannot break down certain fats and this leads to a a toxic buildup of fatty substances in the body's cells and tissues. Inheritance is autosomal recessive. Enzyme replacement therapy for both Wolman disease and cholesteryl ester storage disease is currently approved for use in the United States, European Union, and Japan.