Sitosterolemia: A Rare Cause of Severe Hypercholesterolemia in Children.

INTRODUCTION: Severe hypercholesterolemia in children is commonly caused by familial hypercholesterolemia (FH); however, sitosterolemia, a rare autosomal recessive disorder, should be considered when FH genetic testing is negative. CASE PRESENTATION: A 4-year-old boy presented with xanthomas on his knees. His total cholesterol was 561 mg/dL. Initially, homozygous FH was suspected, and rosuvastatin was started; however, genetic testing was negative. Subsequent genetic testing identified a homozygous ABCG8 variant, consistent with sitosterolemia. Rosuvastatin was discontinued, and ezetimibe and dietary plant sterol restriction were initiated, resulting in significant improvement in cholesterol levels and resolution of xanthomas. DISCUSSION: Sitosterolemia results from impaired ABCG5/8 transporter function, leading to plant sterol accumulation, which can cause hypercholesterolemia, xanthomas, and hematologic abnormalities. Diagnosis is established by demonstrating elevated plant sterol levels or through genetic testing. Treatment involves dietary plant sterol restriction and ezetimibe. CONCLUSIONS: Sitosterolemia, though rare, should be considered in severe hypercholesterolemia when FH genetic testing is negative. This case demonstrates a typical presentation and favorable response to treatment with ezetimibe and dietary modification.