A 40-year-old man has tuberoeruptive xanthomas over the elbows and striking orange-yellow striations of both palms. Lipid profile shows total cholesterol 340 mg/dL, triglycerides 550 mg/dL, LDL 110 mg/dL, and HDL 30 mg/dL. Ultracentrifugation reveals accumulation of cholesterol-rich VLDL remnants (beta-VLDL). Homozygosity for which apolipoprotein isoform is the classic underlying defect?

• A Apolipoprotein C-II (frameshift mutation)
• B Apolipoprotein B100 (Arg3500 replaced by glutamine)
• C Apolipoprotein A-I (truncated variant)
• D Apolipoprotein E2 (Arg158 replaced by cysteine) ✓

Explanation

Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) classically arises in apolipoprotein E2/E2 homozygotes. ApoE2 binds hepatic LDL receptor and LRP poorly, impairing remnant clearance and causing accumulation of IDL and chylomicron remnants as beta-VLDL. Palmar xanthomas are highly characteristic. ApoB3500 mutation causes familial defective apoB100 with isolated high LDL, and apoC-II deficiency causes severe fasting chylomicronemia, killing options B and A.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.