A 40-year-old man has tuberous xanthomas over the elbows and orange-yellow linear deposits in the palmar creases. Fasting lipids show total cholesterol 310 mg/dL, triglycerides 290 mg/dL, LDL near normal, and a prominent broad beta band on electrophoresis. The most likely genetic basis is:

• A Loss-of-function mutation in the LDL receptor
• B Homozygous apolipoprotein E2 (Arg158Cys) causing defective hepatic remnant clearance ✓
• C Apolipoprotein C-II deficiency
• D Gain-of-function mutation in PCSK9

Explanation

Familial dysbetalipoproteinemia (type III) results from homozygous apoE2, which binds the hepatic LDL receptor and LRP poorly, so chylomicron remnants and IDL accumulate. The signature combination of equal elevations in cholesterol and triglyceride around 300 mg/dL, palmar xanthomas, and a broad beta band is diagnostic. LDL receptor defects raise LDL selectively, and apoC-II deficiency causes massive hypertriglyceridemia with pancreatitis instead.

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.