Cholesterol ester storage disease of ..., (Cholesterol ester storage disease) - Gen LIPA

Storage disease cholesterol ester is a rare congenital disorder affecting the metabolism of lipids in the body. In affected individuals, harmful amounts of lipids in cells and tissues throughout the body accumulate. The liver is most intensely affected, resulting in hepatomegaly and hepatic cirrhosis. Usually it develops at an early age atherosclerosis, narrowing arteries, with possible blockage that can lead to a heart attack or stroke.

Symptoms of the disease storage of cholesterol esters are highly variable. Some people have mild symptoms and are not diagnosed until late adulthood, while others may have liver dysfunction in early childhood. The life expectancy of people with storage of cholesterol esters disease depends on the severity of the associated complications.

This disease is due to mutations in the LIPA gene, located on the long arm of chromosome 10 (10q23.2-q23.3) encoding the lysosomal acid lipase enzyme. This enzyme is found in the lysosomes of cells where lipids such as cholesterol esters and triglycerides decompose. In the body, cholesterol binds with high density lipoproteins (HDL). High - density lipoproteins carry cholesterol from the body's tissues to the liver for metabolism. Cholesterol bound to a fatty acid corresponding to cholesteryl esters, which lysosomal acid lipase cholesterol and a fatty acid are degraded.

They described more than 20 mutations in the gene LIPA in people with storage disease cholesterol esters. Most of these mutations change individual amino acids in lysosomal acid lipase and diminish the functional capacity of the protein. LIPA most frequent mutation responsible for the disease is a splice site mutation, in which the guanine nucleotide is replaced by the adenine nucleotide near the LIPA gene exon 8 (IVS8-1G> A). This mutation alters the way in which the enzyme is encoded, which results in a deletion of 24 amino acids. People with IVS8-1G> mutation in both copies of the gene in each cell have only 5 percent of the normal amount of lysosomal lipase activity. A deficiency of lysosomal acid lipase prevents the body to properly metabolize lipids. No activity lysosomal acid lipase, cholesterol esters remain in the blood and tissues, and are not be transported to the liver for excretion. The resulting accumulation of triglycerides, cholesterol esters and other fats inside the cells and tissues leading to the signs and symptoms of the disease storage of cholesterol esters.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have the mutation for disease to occur. The parents of an individual with an autosomal recessive disease, each has a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with storage disease cholesterol esters by the complete PCR amplification of the exons of the gene LIPA, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).