Hyperlipidemia is characterized by increased levels of lipoproteins in the plasma. This disease can be due to a genetic disorder resulting in abnormalities in the lipoprotein metabolism caused by mutations in apoproteins, lipoprotein receptors or lipoprotein lipase. The most common types of hyperlipidemia and their characteristics are depicted in the graphics and discussed below. Familial chylomicronemia (type I hyperlipidemia) is caused by missense mutations in lipoprotein lipase or apoC-II. Xanthomas, lipemia retinalis and increased risk of pancreatitis are associated with this type of hyperlipidemia. Familial hypercholesterolemia (type IIa hyperlipidemia) is known to be caused by defective LDL-receptors (LDL-R).
Tendon xanthomas, tuberous xanthomas and xanthelasmas are the most obvious clinical signs. The fat deposits can also occur in walls of blood vessels causing atherosclerosis and subsequent cardiovascular diseases. Familial defective apoB (type IIb hyperlipidemia) is due to a missense mutation in apoB thereby reducing the affinity of LDL for its receptor and thus impairing LDL catabolism. The signs and symptoms are similar as with familial hypercholesterolemia. Familial dysbetalipoproteinemia (type III hyperlipidemia) is characterized by a genetic disorder of the apoE. Clinical symptoms include tuberous xanthomas, striae palmaris and peripheral vascular disease. Patients have an increased risk of atherosclerosis.
Secondary hyperlipidemias can be caused by:
Extra info: Metabolic/endocrine diseases and certain drugs can cause secondary hyperlipidemia. Heart failure, tachycardia and diabetes insipidus are not known to induce secondary hyperlipidemia.
Which of the following is the primary defect in familial hypercholesterolemia?