Cholesteryl ester storage disease

Cholesteryl ester storage disease is a rare inherited condition involving the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of lipids accumulate in cells and tissues throughout the body. The liver is most severely affected. An enlarged liver (hepatomegaly) is one of the key signs of the disease. In addition, chronic liver disease (cirrhosis) can develop. An accumulation of fatty deposits on the artery walls (atherosclerosis) is usually seen early in life. The deposits narrow the arteries and can eventually block them, increasing the chance of having a heart attack or stroke.

The symptoms of cholesteryl ester storage disease are highly variable. Some people have such mild symptoms that they go undiagnosed until late adulthood, while others can have liver dysfunction in early childhood. The expected lifespan of those with cholesteryl ester storage disease depends on the severity of the associated complications.

Cholesteryl ester storage disease appears to be a rare disorder. About 50 individuals affected by this condition have been reported worldwide.

Mutations in the LIPA gene cause cholesteryl ester storage disease.

The LIPA gene provides instructions for making an enzyme called lysosomal acid lipase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it breaks down lipids such as cholesteryl esters and triglycerides.

In the body, cholesterol works with high-density lipoproteins (HDL), often referred to as "good cholesterol." High-density lipoproteins carry cholesterol from the body's tissues to the liver for removal. When the cholesterol is attached to a fatty acid it is a cholesteryl ester. Normally, cholesteryl esters are broken down by lysosomal acid lipase into cholesterol and a fatty acid. Then the cholesterol can be transported by HDL to the liver for removal.

Mutations in the LIPA gene lead to a shortage of lysosomal acid lipase and prevent the body from using lipids properly. Without the activity of lysosomal acid lipase, the cholesteryl esters stay in the blood and tissues and are not able to be transported to the liver for excretion. The resulting buildup of triglycerides, cholesteryl esters, and other fats within the cells and tissues cause the signs and symptoms of cholesteryl ester storage disease.

Read more about the LIPA gene.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.