Clinical scenario: Yellowish skin lesions | Family history of ischemic heart disease
An 8-year-old boy is brought to the pediatric outpatient department because of multiple painless yellowish skin lesions over both elbows, knees, and the Achilles tendons that have gradually increased in size over the past 2 years. He is otherwise healthy and has normal growth and development. His father died suddenly from myocardial infarction at 38 years of age, and his paternal grandfather underwent coronary artery bypass surgery before the age of 50 years.
On examination, the lesions are firm, non-tender tendon xanthomas. Cardiovascular examination is unremarkable.
Which of the following is the most likely diagnosis?
A. Cerebrotendinous xanthomatosis
B. Familial hypercholesterolemia
C. Sitosterolemia
D. Tangier disease
E. Wolman disease
Correct answer & Explanation:
Correct Answer: B. Familial hypercholesterolemia
Explanation:
Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused most commonly by mutations in the LDL receptor (LDLR) gene, resulting in markedly elevated LDL cholesterol from birth.
The diagnosis should be suspected in a child with:
- Tendon xanthomas (Achilles tendon, extensor tendons of the hands, elbows, knees)
- Strong family history of premature coronary artery disease
- Normal triglyceride levels
- Markedly elevated LDL cholesterol
The presence of tendon xanthomas in childhood is highly suggestive of heterozygous FH, while extensive xanthomas appearing in early childhood with extremely high LDL levels raise concern for homozygous FH.
Why the Other Options Are Incorrect
A. Cerebrotendinous xanthomatosis
- Tendon xanthomas occur but are associated with progressive neurological dysfunction, cataracts, and chronic diarrhea, not isolated hypercholesterolemia.
C. Sitosterolemia
- May resemble FH clinically but is rare and caused by increased absorption of plant sterols. Diagnosis requires elevated plasma plant sterols.
D. Tangier disease
- Characterized by very low HDL cholesterol, orange tonsils, hepatosplenomegaly, and peripheral neuropathy rather than tendon xanthomas.
E. Wolman disease
- Presents in infancy with adrenal calcification, diarrhea, failure to thrive, and hepatosplenomegaly.
High-Yield Pearls
- Inheritance: Autosomal dominant
- Most common gene: LDLR
- Less common genes: APOB and PCSK9
- Typical lesion: Tendon xanthoma
- Lipid profile: Markedly elevated LDL cholesterol with normal triglycerides
- Major complication: Premature atherosclerotic cardiovascular disease
- First-line treatment in children:
- Diet and lifestyle modification
- Statin therapy (usually initiated from 8–10 years of age in heterozygous FH)
Exam Pearl
A child presenting with:
- Tendon xanthomas
- Family history of premature myocardial infarction
- Markedly elevated LDL cholesterol
→ Think Familial Hypercholesterolemia (LDL receptor defect).
