An infant with a heterozygous variant of ABCG5 presented with hypercholesterolemia only during breastfeeding.

Sitosterolemia (OMIM #210250) is a rare lipid disorder caused by variants in genes encoding adenosine triphosphate (ATP)-binding cassette subfamily G Member 5 (ABCG5) or 8 (ABCG8), which play roles in the intestinal and biliary excretion of cholesterol and plant sterols, such as sitosterol and campesterol. Although considered an autosomal recessive disorder, recent reports have shown that a heterozygous ABCG5 variant can also cause mild symptoms. Here, we report the case of an infant with a heterozygous variant of ABCG5. A 6-mo-old breast-fed Japanese male infant was found to have elevated serum total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels of 528 mg/dL and 449 mg/dL, respectively, upon examination for growth disturbances. As weaning progressed, the cholesterol levels normalized. Genetic analysis revealed that the patient and his mother had the heterozygous variant c.1166G>A (p.Arg389His) in ABCG5. Compared to his father, who did not have the ABCG5 variant, the patient and his mother had mild elevations of serum sitosterol and campesterol. Serum sitosterol and campesterol levels were 9.6 and 12 μg/mL for the patient, 4.9 and 9.3 μg/mL for his mother, and 2.1 and 3.4 μg/mL for his father, respectively. Therefore, heterozygous variants of ABCG5 may lead to transient hypercholesterolemia during breastfeeding.