Plant sterol hyperabsorption caused by uncontrolled diabetes in a patient with a heterozygous ABCG5 variant.

ABSTRACT

Plant sterol intake is widely recommended for patients with cardiovascular risk factors based on the inhibitory effect on intestinal cholesterol absorption. Although plant sterols, once absorbed, can promote atherosclerosis, their intake is believed to be safe because of poor absorption, except in rare hyperabsorbers with homozygous ABCG5/8 mutations. We report a case of new-onset type 1 diabetes accompanied by hypercholesterolemia. At the initial presentation with diabetic ketoacidosis, the patient showed marked hypercholesterolemia. Whole-exome sequencing revealed a heterozygous pathogenic variant in ABCG5 (p.R419H). The initial serum plant sterol levels were markedly high (sitosterol 32.5 µg/mL, campesterol 66.0 µg/mL), close to the range observed in patients with homozygous ABCG5/8 mutations, which were largely reduced by insulin treatment without ezetimibe. The addition of ezetimibe normalized plant sterol levels. These findings provide the first evidence that uncontrolled diabetes plays a causal role in the pathogenesis of phytosterolemia.