Severe Multivessel Coronary Artery Disease in an Adolescent With Genetic Dyslipidemia

Familial hypercholesterolemia is characterized by lifelong elevations in low-density lipoprotein cholesterol (LDL-C) that, when left untreated, markedly increase the risk of premature atherosclerotic cardiovascular disease (ASCVD). Although ASCVD is common in adults with familial hypercholesterolemia, events in adolescence are rare.

A 14-year-old man presented with exertional chest pain and mild troponin elevation. Myocarditis was initially suspected, but the persistence of symptoms prompted advanced imaging, revealing multivessel ASCVD. LDL-C was severely elevated (9 mmol/L, 350 mg/dL). Atorvastatin and ezetimibe lowered LDL-C to ≤1.4 mmol/L (<55 mg/dL). Multivessel percutaneous coronary intervention resulted in resolution of symptoms and inducible ischemia. A heterozygous APOE p.(Leu167del) pathogenic variant was identified, an uncommon cause of heterozygous familial hypercholesterolemia (HeFH). Similarly severe dyslipidemia was identified in the 6-year-old brother.

This particularly aggressive and genetically unique form of HeFH resulted in premature ASCVD from adolescence.

Early detection and treatment prevent catastrophic cardiovascular events in HeFH; cascade screening is essential for at-risk relatives.