Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Lecithin-Cholesterol Acyltransferase (LCAT) Deficiency [E78.6]

OMIM numbers: 245900, 606967 (LCAT)

Dr. med. Hanns-Georg Klein

Scientific Background

Primary LCAT deficiency is a rare, autosomal recessive enzyme defect of the extracellular cholesterol metabolism. LCAT is secreted by the liver and is responsible for the esterification of free cholesterol in the blood. LCAT deficiency has been associated with impaired maturation or metabolism of the HDL particles so that immature HDL precursors accumulate. A major sign is hypoalphaliproteinemia (HDL-C < 10 mg/dl) accompanied by corneal opacity (not to be confused with arcus lipoides). Besides mild, reactive hypertriglyceridemia, a reduced proportion of cholesterol esters in the total cholesterol (< 60%) is characteristic. Moreover, atypical lipoproteins (e.g. LpX) can be detected. In the course of the disease, lipid deposition causes glomerulosclerosis, which may result in renal insufficiency as well as normochromic anemia, caused by reduced osmotic resistance of erythrocytes. Fish Eye Disease, however, which is caused by a partial LCAT deficiency, has not been associated with glomerulosclerosis and anemia.

The molecular cause for LCAT deficiency is mutations in the LCAT gene on chromosome 6. So far, more than 70 mutations, spread over the entire gene, have been identified. An enzyme replacement therapy is currently being tested. Recent studies have shown that LCAT deficiency is accompanied by an increased risk for coronary heart disease as well. Regarding a differential diagnosis, LCAT deficiency should be differentiated from Apo-A-I and ABCA1 deficiency (Tangier disease), which have also been associated with hypoalphalipoproteinemia. These diseases, however, exhibit a significantly higher risk for coronary heart disease.