Sitosterolemia presenting with severe hypercholesterolemia and intertriginous xanthomas in a breastfed infant: case...

Sitosterolemia is an autosomal recessive disorder characterized by increased intestinal absorption of plant sterols. It is caused by mutations in genes encoding ATP-binding cassette, subfamily G5 (ABCG5) or G8 (ABCG8), and clinical features include elevated plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, patients with sitosterolemia also hyperabsorb cholesterol, and serum cholesterol levels tend to be elevated.

We report an infant with sitosterolemia who presented with severe hypercholesterolemia and intertriginous xanthomas.

A 15-month-old Korean girl presented with yellow dermal plaques over flexural areas including the wrist, neck, and gluteal folds, which were consistent with intertriginous xanthomas. The lesions were first noticed at 3 months of age when she was being exclusively breastfed. Her total cholesterol and low-density lipoprotein-cholesterol levels were 675 and 540 mg/dL, respectively. A low-fat/low-cholesterol diet and cholestyramine therapy were introduced. Unexpectedly, her serum cholesterol level decreased dramatically and normalized in 2 months. Cholestyramine was tapered off. The xanthomas also regressed and disappeared by 3 years of age. Gas chromatography-mass spectrometric analysis was performed with serum drawn at 3 years of age when her low-density lipoprotein-cholesterol was 118 mg/dL, which revealed striking elevation of her sitosterol level at 19.36 mg/dL. Direct sequencing for ABCG5 revealed compound heterozygous null mutations c.904+1G>A (p.Met302Asnfs*82) and c.1336C>T(p.Arg446*).

Our case suggests that sitosterolemia can present with severe hypercholesterolemia and intertriginous xanthomas. Sitosterolemia should be suspected when a patient with hypercholesterolemia shows unexpectedly good response to dietary modification or bile acid sequestrant therapy.