Summary
Cholesterol circulates in the bloodstream in transporters called lipoproteins. Lipoproteins (low-density proteins or LDL) carry about 2/3 of plasma cholesterol every day and deliver it to every cell in the organism. A specific recognition mechanism (similar to a key in a keyhole) allows apolipoprotein B, a backbone-protein of LDL, to recognize receptors at the cell surface: LDL receptors. Cells use this mechanism to take up LDL and use their cholesterol content to built-up new molecules (like steroid hormones) or to maintain their membranes in good shape. Genetic mutations of the Apolipoprotein at its site of recognition for LDL receptors B (defining familial defective apo B-100), prevent LDL from being taken up by cells. LDL accumulate in plasma and in the arterial wall. Patients are unaware of their condition due to the lack of alerting symptoms. Plasma cholesterol may be elevated from childhood and contributes to the development of atherosclerosis. Consequently, familial defective apolipoprotein B-100 causes cardiovascular disease (myocardial infarction) before age 50. The disease is diagnosed on the grounds of clinical signs (cholesterol skin deposits, called xanthoma) and of the biological lipid profile, but genetic testing formally identifies the causative mutation. One in every two persons is affected in a family where one individual has been identified as having a familial apo B-100 deficiency. It has been shown that about 1/3 of patients with familial defective apolipoprotein B-100, may have sometimes low to normal plasma cholesterol levels, although themselves may become hypercholesterolemic or their relatives may be severely affected. Therefore, once an individual is identified in the family, it is important to identify other mutation carriers in the family. Once the diagnosis is established, drug therapy (adapted for each age and case) brings the levels of plasma cholesterol back to normal preventing cardiovascular disease. The disease frequency is estimated between 1/200 and 1/1200 births in populations originating from central-western Europe. The disease is also found in Asia. * Author: P. Benlian, M.D., Ph.D. (September 2000) *
