Familial hypercholesterolemia is a "receptor disease" that is the consequence of a mutation in the gene encoding the receptor for low density lipoprotein (LDL), which is involved in the transport and metabolism of cholesterol.

As a consequence of receptor abnormalities, there is a loss of feedback control and elevated levels of cholesterol that induce premature atherosclerosis, leading to a greatly increased risk of myocardial infarction.

Familial hypercholesterolemia is possibly the most frequent mendelian disorder. Heterozygotes with one mutant gene, representing about 1 in 500 individuals, have from birth a twofold to threefold elevation of plasma cholesterol level, leading to tendinous xanthomas and premature atherosclerosis in adult life.

Homozygotes, having a double dose of the mutant gene, are much more severely affected and may have fivefold to sixfold elevations in plasma cholesterol levels. These individuals develop skin xanthomas and coronary, cerebral, and peripheral vascular atherosclerosis at an early age.

Myocardial infarction may develop before age 20. Large-scale studies have found that familial hypercholesterolemia is present in 3% to 6% of survivors of myocardial infarction.