Isolated thrombocytopenia as an atypical presentation of sitosterolemia in a school-aged child

Sitosterolemia is a rare autosomal recessive lipid metabolism disorder caused by excessive intestinal absorption and impaired hepatic excretion of plant sterols and cholesterol. The condition caused by mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) gene or the ATP-binding cassette subfamily G member 8 (ABCG8) gene is typically characterized by the presence of xanthomas, early-onset atherosclerosis, and hemolytic anemia. Hematological abnormalities including thrombocytopenia have been reported in patients with sitosterolemia, and may occasionally occur in the absence of dyslipidemia or xanthomas. We present the case of a 6-year-old girl diagnosed with sitosterolemia following the detection of isolated thrombocytopenia during a routine school health screening. Laboratory investigations revealed markedly elevated plasma plant sterol levels; however, dyslipidemia, which is a common feature of this disease, was absent in this case. Although platelet abnormalities have previously been reported in patients with sitosterolemia, the distinguishing feature of this case is the presentation of thrombocytopenia that responded to ezetimibe therapy. The platelet count increased from 58,000/mm³ prior to treatment to 117,000/mm³ following therapy, and further improved to 140,000/mm³ at the most recent follow-up visit. Genetic analysis identified a homozygous pathogenic variant in ABCG5 (c.161G>A, p.Trp54Ter), confirming the diagnosis. This case highlights the significance of thrombocytopenia responsive to ezetimibe as a primary presentation of sitosterolemia, even in the absence of dyslipidemia. In conclusion, it emphasizes the importance of considering sterol metabolism disorders in the differential diagnosis of unexplained thrombocytopenia.