Clinical features of familial hypercholesterolemia.

The clinical consequences of familial hypercholesterolemia (FH) result from its metabolic peculiarities that persist from very early childhood, leading to the accumulation of cholesterol in the form of xanthomas in skin and tendons and atheromatous lesions in the arterial wall, in particular, in the aorta and the stem of coronary arteries. Plasma cholesterol concentration markedly increases during the suckling period, soon attaining a level near 1000 mg/dl in homozygotes and 200 to 400 mg/dl in heterozygotes. By age 50, about 80% of FH males suffer from ischemic heart diseases, while only 20% to 30% of the females are moderately affected by coronary atherosclerosis. In addition to the low density lipoprotein (LDL) cholesterol level, higher triglyceride and lower high density lipoprotein (HDL) cholesterol levels correlate with an increased risk of ischemic heart diseases. A very important problem is that most of these patients do not feel themselves to be seriously ill until a severe myocardial infarction (often leading to sudden death) takes place during the third to fifth decades of life. Among the different types of receptor mutations, the incidence of ischemic heart diseases was much higher and more extensive among patients with the receptor-negative type than among those with the receptor-defective type with a residual receptor activity.