Random Dermatology MCQ - Familial Hypercholesterolemia (FH)

A 60-year-old man presents with asymptomatic, waxy, yellow-orange plaques in his palmar creases and along the tendons of his hands. He has a history of premature coronary artery disease. Laboratory studies show total cholesterol 380 mg/dL and LDL 310 mg/dL. Which of the following is the most likely underlying genetic defect?

A) LDL receptor deficiency
B) Lipoprotein lipase deficiency
C) ApoE2 homozygosity
D) Hepatic lipase deficiency
E) ABCA1 transporter mutation

Correct Answer: A) LDL receptor deficiency

Explanation

Key Features of Familial Hypercholesterolemia (FH):

1. Clinical Presentation:

   • Tendon xanthomas (Achilles, extensor tendons of hands)

   • Xanthelasma palpebrarum (eyelid plaques)

   • Arcus cornealis (<45 years old)

   • Premature cardiovascular disease (often <55 years)

2. Laboratory Findings:

   • Markedly elevated LDL (>190 mg/dL in adults)

   • Normal triglycerides

   • Autosomal dominant inheritance

3. Pathogenesis:

   • LDL receptor defect (most common in FH) → impaired LDL clearance

   • Results in cholesterol deposition in tendons (xanthomas) and arteries

Why Not Other Options?

• (B) Lipoprotein lipase deficiency: Causes type I hyperlipoproteinemia (milky plasma, eruptive xanthomas)

• (C) ApoE2 homozygosity: Causes type III dysbetalipoproteinemia (palmar xanthomas, elevated IDL)

• (D) Hepatic lipase deficiency: Rare, causes combined hyperlipidemia

• (E) ABCA1 mutation: Causes Tangier disease (orange tonsils, low HDL)

Management:

1. High-intensity statin (atorvastatin 80 mg or rosuvastatin 40 mg)

2. Ezetimibe or PCSK9 inhibitor adjunct

3. LDL apheresis for refractory cases

Prognosis: Untreated leads to myocardial infarction by age 50 in homozygous FH.