What is the presumed defect in most cases of familial type IIa hyperlipoproteinemia?

What is the presumed defect in most cases of familial type IIa hyperlipoproteinemia?

• A. Defective receptors for LDL
• B. Deficiency of hydroxymethylglutaryl (HMG)-CoA reductase
• C. Deficiency of cholesterol esterase
• D. Deficiency of LPL

Answer: (A)

Familial type IIa hyperlipoproteinemia is due to defective clearance of LDL from the blood. The liver uses LDL receptors to bind and internalize LDL particles via apoB-100; when these receptors are defective, LDL stays in circulation and plasma LDL cholesterol rises markedly, driving early atherosclerosis. This mechanism fits the pattern seen in this condition, whereas a deficiency of HMG-CoA reductase would reduce cholesterol synthesis rather than raise LDL levels. Deficiency of cholesterol esterase or lipoprotein lipase would produce different lipid profiles (not the isolated LDL elevation typical of this disorder). So the best explanation is that receptors for LDL are defective.

Familial type IIa hyperlipoproteinemia is due to defective clearance of LDL from the blood. The liver uses LDL receptors to bind and internalize LDL particles via apoB-100; when these receptors are defective, LDL stays in circulation and plasma LDL cholesterol rises markedly, driving early atherosclerosis. This mechanism fits the pattern seen in this condition, whereas a deficiency of HMG-CoA reductase would reduce cholesterol synthesis rather than raise LDL levels. Deficiency of cholesterol esterase or lipoprotein lipase would produce different lipid profiles (not the isolated LDL elevation typical of this disorder). So the best explanation is that receptors for LDL are defective.