Sitosterolemia 2

Any sitosterolemia caused by a variation in the ABCG5 gene, characterized by markedly increased intestinal absorption and reduced biliary excretion of plant sterols, resulting in extremely elevated plasma sitosterol levels, tendon and tuberous xanthomas, and premature atherosclerosis. A subset of affected individuals develop hematologic manifestations, including stomatocytic hemolysis, macrothrombocytopenia, splenomegaly, and abnormal bleeding, and in some cases these hematologic findings may be the initial or only clinical signs. Biallelic loss‑of‑function variants in ABCG5 impair the heterodimeric ABCG5/ABCG8 transporter required for limiting dietary sterol uptake and promoting biliary excretion, leading to membrane sterol accumulation in multiple blood cell types.