A patient presented with tendon xanthomas. His lipid profile showed serum cholesterol levels to be 283 mg/dL and serum LDL to be 202 mg/dL. He was started on lovastatin. What is the likely diagnosis?

Correct Answer: B. Familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by defective or absent LDL receptors, leading to severely elevated LDL cholesterol and premature atherosclerosis. The clinical presentation here is pathognomonic: tendon xanthomas (lipid deposits in tendons, especially Achilles and extensor tendons of hands) are a hallmark of FH and rarely occur in other dyslipidemias. The lipid profile showing total cholesterol 283 mg/dL with LDL 202 mg/dL (markedly elevated, typically >160 mg/dL in heterozygotes) confirms the diagnosis. Lovastatin, an HMG-CoA reductase inhibitor (statin), is the first-line pharmacological agent for FH in India, as it reduces hepatic cholesterol synthesis and upregulates LDL receptors. Heterozygous FH affects 1 in 500 Indians; homozygous FH (1 in 1,000,000) presents with xanthomas in childhood and coronary events before age 20. The presence of tendon xanthomas distinguishes FH from other hyperlipidemias and mandates aggressive lipid-lowering therapy per Indian guidelines (ICMR, Cardiological Society of India) to prevent premature coronary artery disease.

Why the other options are wrong

A. Familial hyperchylomicronemia — This is wrong because familial hyperchylomicronemia (Type I hyperlipoproteinemia) is caused by lipoprotein lipase deficiency and presents with markedly elevated triglycerides (often >1000 mg/dL), not cholesterol. Patients develop eruptive xanthomas (small, yellow papules on buttocks/elbows) and lipemic plasma, not tendon xanthomas. LDL is typically normal or low. Lovastatin is contraindicated in this condition. C. Lipoprotein lipase deficiency — This is wrong because lipoprotein lipase deficiency causes Type I hyperlipoproteinemia with severe hypertriglyceridemia (>1500 mg/dL), not hypercholesterolemia. Cholesterol levels are normal or low. Clinical features include eruptive xanthomas, hepatosplenomegaly, and recurrent pancreatitis—not tendon xanthomas. The lipid pattern here (high LDL, normal triglycerides) excludes this diagnosis. D. Tangier's disease — This is wrong because Tangier disease is a rare autosomal recessive disorder of HDL metabolism (ABCA1 transporter defect) presenting with very low HDL, normal or low LDL, and orange-yellow tonsillar discoloration—not tendon xanthomas. Cholesterol levels are typically low-normal. The markedly elevated LDL (202 mg/dL) and tendon xanthomas are incompatible with Tangier disease.

High-Yield Facts

Mnemonics

TENDON = FH Tendon xanthomas → Familial Hypercholesterolemia. When you see tendon xanthomas on exam, think FH first. No other dyslipidemia causes them. FH Xanthoma Types (by LDL level) Tendon (FH, LDL >160) | Eruptive (Type I, TG >1000) | Planar (Type III, remnant disease). Tendon = FH is the key discriminator.

NBE Trap

NBE pairs "elevated cholesterol + xanthomas" with multiple options to trap students who confuse xanthoma types. The key discriminator is tendon xanthomas, which are pathognomonic for FH and absent in hyperchylomicronemia (eruptive) and lipoprotein lipase deficiency (eruptive/hepatosplenomegaly).

Clinical Pearl

In Indian clinical practice, FH is often underdiagnosed because tendon xanthomas are mistaken for rheumatoid nodules or other benign lesions. Any patient presenting with tendon xanthomas + LDL >160 mg/dL should be screened for FH and started on statins immediately to prevent premature MI (common in Indian males by age 40–50 with FH).

_Reference: KD Tripathi Ch. 24 (Lipid-Lowering Drugs); Robbins Ch. 5 (Genetic Disorders); Harrison Ch. 356 (Lipoprotein Disorders)_