Contributor: Gordon K. Klintworth
Familial hypercholesterolemia is one of the most frequent inherited disorders. It is an autosomal dominant heterogenous inherited disorder of lipid metabolism characterized by hypercholesterolemia, elevated LDL particles in plasma that leads to premature death from complications of atherosclerosis. The complications involve the cardiovascular system and include occlusovascular disease, cerebral infarction [infarction - brain], and myocardial infarction [infarction - myocardium]. Ophthalmic manifestations include arcus lipoides, xanthoma of the eyelid, and retinal occlusovascular disease [occlusovascular disease - retina]. Familial hypercholesterolemia results from several different metabolic defects in the cell-surface receptors that remove LDL particles from plasma. These defects relate to mutations in several genes, including FH3, LDLR, and APOB. More than 600 mutations in the LDLR have been detected in LDL receptor defect, and three mutations in APOB have been detected in familial ligand-defective apoprotein B-100 hypercholesterolemia.