Familial apolipoprotein E deficiency.
A unique kindred with premature cardiovascular disease, tubo-eruptive xanthomas, and type III hyperlipoproteinemia (HLP) associated with familial apolipoprotein (apo) E deficiency was examined. Homozygotes (n = 4) had marked increases in cholesterol-rich very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL), which could be effectively lowered with diet and medication (niacin, clofibrate). Homozygotes had only trace amounts of plasma apoE, and accumulations of apoB-48 and apoA-IV in VLDL, IDL, and low density lipoproteins. Radioiodinated VLDL apoB and apoE kinetic studies revealed that the homozygous proband had markedly retarded fractional catabolism of VLDL apoB-100, apoB-48 and plasma apoE, as well as an extremely low apoE synthesis rate as compared to normals. Obligate heterozygotes (n = 10) generally had normal plasma lipids and mean plasma apoE concentrations that were 42% of normal. The data indicate that homozygous familial apoE deficiency is a cause of type III HLP, is associated with markedly decreased apoE production, and that apoE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000172:deficiency*; D002648:Child; D002784:Cholesterol / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood / Q000150:complications / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010743:Phospholipids / Q000097:blood; D012016:Reference Values; D012871:Skin Diseases / Q000209:etiology; D014280:Triglycerides / Q000097:blood; D014973:Xanthomatosis / Q000209:etiology
D001057:Apolipoproteins E; D008074:Lipoproteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol