Familial hypercholesterolemia

A dominantly inherited genetic condition that results in markedly elevated LDL (low-density lipoprotein) cholesterol levels beginning at birth, and cause heart attacks at an early age.

Type II hyperlipoproteinemia; Hypercholesterolemic xanthomatosis; Low density lipoprotein receptor mutation

Affected people have consistently high levels of low-density lipoprotein (LDL or "bad" cholesterol), which leads to premature atherosclerosis of the coronary arteries. Typically in affected men, heart attacks occur in their 40s to 50s, and 85% of men with this disorder have experienced a heart attack by age 60. The incidence of heart attacks in women with this disorder is also increased, but happens 10 years later than in men.

Individuals from families with a strong history of early heart attacks should be evaluated with a lipid screen. Proper diet, exercise, and the use of newer drugs can bring lipids (fats in the blood) down to safer levels.

The mutation that causes this genetic abnormality occurs on chromosome 19. It is possible for a person to inherit copies of the mutated gene for this disorder (one from each parent, making them genetically "homozygous").

In homozygous individuals the condition is more severe, and cholesterol values may exceed 600 mg/dL. These individuals develop waxy plaques (xanthomas) beneath the skin over their elbows, knees, buttocks. These are deposits of cholesterol in the skin. In addition, they develop deposits in tendons and around the cornea of the eye. Atherosclerosis begins before puberty and heart attacks and death may occur before age 30, or they may require highly invasive surgery such as a liver transplant.

Those who have inherited only one copy of the mutated gene (from one parent) are called heterozygous. These individuals may respond well to diet modifications combined with statin drugs.