Hyperlipidemias are disorders of the rates of synthesis or clearance of lipoproteins from the bloodstream. Usually they are detected by measuring plasma triacylglycerol and cholesterol and are classified on the basis of which class of lipoproteins is elevated.
Type I hyperlipidemia is due to accumulation of chylomicrons. Two genetic forms are known: lipoprotein lipase deficiency and ApoC-2 deficiency. Apoc-2 is required by lipoprotein lipase for full activity. Patients with type 1 hyperlipidemia have exceedingly high plasma triacylglycerol concentrations and suffer from eruptive xanthomas and pancreatitis.
Type II hyperlipidemia is characterized by elevated LDL levels. Most cases are due to genetic defects in the synthesis, processing, or function of the LDL receptor. Heterozygotes have elevated LDL levels; hence the trait is dominantly expressed. Homozygous patients have very LDL levels and may suffer myocardial infarctions before age 20.
Type III hyperlipidemia is due to abnormalities of ApoE, which interfere with the uptake of chylomicron and VLDL remnants. Hypothyroidism can produce a very similar hyperlipidemia. These patients have an increased risk of atherosclerosis.
Type IV hyperlipidemia is the commonest abnormality. The VLDL levels are increased, often due to obesity, alcohol abuse, or diabetes. Familial forms are also known but the molecular defect is unknown.
Type V hyperlipidemia is, like type I, associated with high chylomicron triacylglycerol levels, pancreatitis, and eruptive xanthomas.
Hypercholesterolemia also occurs in certain types of liver disease in which biliary excretion of cholesterol is reduced. An abnormal lipoprotein called lipoprotein X accumulates. This disorder is not associated with increased cardiovascular disease from atherosclerosis.