A patient with familial hypercholesterolemia has a mutation in the APOB gene. This mutation affects the structure of apolipoprotein B-100, specifically preventing its effective binding to the LDL receptor, but does not interfere with its role in VLDL assembly and secretion from the liver. Which metabolic profile is most consistent with this specific defect?
- Reduced secretion of VLDL particles from the liver, leading to low plasma triacylglycerol levels.
- Normal secretion of VLDL from the liver, but elevated plasma concentrations of LDL due to impaired clearance. (correct answer)
- Increased activity of lipoprotein lipase, leading to rapid conversion of VLDL to LDL and low VLDL levels.
- Elevated plasma HDL concentrations as a compensatory mechanism for the defective LDL pathway.
Explanation: ApoB-100 has two key roles: structural integrity for VLDL/IDL/LDL and acting as the ligand for the LDL receptor. The question states that VLDL assembly/secretion is normal, so the liver will produce and secrete VLDL at a typical rate. VLDL will be converted to IDL and then to LDL in circulation. However, because the ApoB-100 on the resulting LDL particle cannot bind to the LDL receptor, clearance of LDL from the blood is severely impaired, leading to high plasma LDL levels.