Clinical features of familial hypercholesterolemia

Familial hypercholesterolemia (FH) is characterized by specific elevation of low density lipoprotein (LDL) level in blood and requires special treatment. 

According to Frederickson's classification FH refers to type IIa or less frequently to type IIb hyperlipoproteinemia. Due to impaired LDL catabolism in persons with FH the blood cholesterol level is very high. In the rare homozygous FH patients (prevalence 1:1 000 000) total blood cholesterol level rises up to 600-1200 mg/dl (15-30 mM). In much more common heterozygous FH patients (prevalence 1:500) the total blood cholesterol level is 280-500 mg/dl (7-12.5 mM). The normal blood cholesterol level is 120-180 mg/dl (3.5-4.5 mM). The common consequence of an elevation of serum cholesterol  is atherosclerosis. Usually atherosclerotic plaques develop in coronary arteries, brain vessels or vessels of the legs. The atherosclerotic lesions can lead to the development of angina pectoris, premature myocardial infarction, ischemic strokes and  intermittent  claudication. Clinical symptoms of ischemic heart disease usually develop by the age of 15-20 in the patients with homozygous familial hypercholesterolemia. The same clinical symptoms develop in the patients with heterozygous familial hypercholesterolemia prior to age of 40. 

The typical clinical signs in  patients with FH include tendon xanthoma, xanthellasma around the eyes and corneal lipid arcus. However, only 25-30% of  patients with heterozygous FH have these features. Thus, in most cases the diagnosis of FH is based on the determination of blood plasma lipids, characteristic blood lipid fractions, on specific clinical features in the patients and on the positive family history of myocardial infarctions. It is noteworthy, that ischemic heart disease develops usually in the grown-ups. The cholesterol level changes significantly in adolescence and grows with age. Thus, the DNA-analysis is the most sensitive and precise method for diagnosis of FH. It is of importance, that identification of FH-causing mutations in the LDL receptor gene can be easily performed in children without developed hyperlipidemia. The DNA-diagnostics is recommended especially in relatives of probands with the clinically established diagnosis of FH. However, the identification of the disease-causing mutation is necessary in each family (see page: Diagnostics).
The early diagnosis of FH, by means of biochemical or genetic methods, allows the physicians to give the patients the adequate treatment (see page: Treatment of FH). This treatment is most effective if timely measures were taken.
We address the specialists and all persons who are interested in the problems of differential diagnosis and treatment of hyperlipoproteinemia to the References  and to comprehensive book: "Clinical lipidology" with the cover you can see on this page. 

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