Novel mutation in sitosterolemia: A rare cause of hyperlipidemia

Sitosterolemia is a rare autosomal recessive disorder characterized by hypercholesterolemia, tendon and tuberous xanthomas, premature atherosclerosis, hemolytic anemia, and macrothrombocytopenia. Hematologic abnormalities are typically detected on routine complete blood counts and are often overlooked. Biochemical studies frequently reveal findings similar to hyperlipidemia. In sitosterolemia, elevated plasma plant sterol levels are observed. Definitive diagnosis can be established by identifying homozygous or compound heterozygous pathogenic variants in ABCG5 and/or ABCG8.

The index case was a 6-year-old Turkish girl referred to our clinic because of elevated total and low-density lipoprotein cholesterol levels detected during follow-up. Physical examination revealed no xanthomas or other abnormal findings. Complete blood count and peripheral blood smear demonstrated anemia, macrothrombocytopenia, and stomatocytosis. Based on the clinical and laboratory findings, sitosterolemia was suspected and subsequently confirmed by detection of a novel homozygous pathogenic variant, exon 2 to 3 deletion, in ABCG8.

Sitosterolemia can be managed with dietary modification and, if necessary, the use of ezetimibe, a sterol absorption inhibitor, if diagnosed early. Sterol levels can be reduced by 10% to 50%. It is crucial to consider sitosterolemia in the differential diagnosis of patients with unexplained hemolytic anemia and macrothrombocytopenia accompanying hyperlipidemia.