A 38-year-old man presents with tuberoeruptive xanthomas over the elbows and striking orange-yellow xanthomas in the palmar creases. Lipid profile shows total cholesterol 310 mg/dL and triglycerides 340 mg/dL. Lipoprotein electrophoresis reveals a broad beta band. The underlying defect is:

• A Gain-of-function mutation in PCSK9
• B Deficiency of apolipoprotein B100
• C Homozygous apolipoprotein E2 with impaired hepatic remnant uptake ✓
• D Deficiency of hepatic triglyceride lipase

Explanation

This is familial dysbetalipoproteinemia (type III hyperlipoproteinemia): homozygosity for apoE2, which binds the hepatic LDL receptor and LRP poorly, causing accumulation of chylomicron remnants and IDL as beta-VLDL, seen electrophoretically as a broad beta band. Palmar (striae) xanthomas are nearly pathognomonic. ApoE2 homozygotes develop overt disease only when a secondary factor such as diabetes, hypothyroidism or obesity coexists. ApoB100 deficiency would lower LDL, and PCSK9 gain-of-function causes isolated severe LDL elevation without remnant accumulation.

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.