title: Sitosterolemia: diagnosis, investigation, and management.
abstract: Sitosterolemia is a rare autosomal recessively inherited disease caused by mutations affecting ABCG5 or ABCG8, which are located on human chromosome band 2p21. Around 100 cases have been reported in the literature. Sitosterolemic patients typically exhibit a 30-fold to 100-fold increase in plasma concentrations of plant sterols. The clinical manifestations include xanthomas, premature atherosclerosis, hemolytic anemia, and macrothrombocytopenia. It is noteworthy that abnormal hematological parameters may be the only clinical feature of sitosterolemic patients, suggesting that sitosterolemia may be more frequent than previously thought. Severe accumulation of plant sterols in mouse models of sitosterolemia induced complex cardiac lesions, anemia, and macrothrombocytopenia, disrupted adrenal and liver cholesterol homeostasis, and caused infertility and hypertriglyceridemia. It remains unclear whether all disease traits are present in sitosterolemic patients. The drug ezetimibe appears to be effective in reducing plasma plant sterol levels, promotes xanthoma regression, and improves the cardiovascular and hematological signs in sitosterolemic patients.
authors.affiliation: Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Sant Antoni Maria Claret 167, 08025, Barcelona, Spain, jescola@santpau.cat.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escolà-Gil
authors.forename: Helena
authors.initials: H
authors.lastname: Quesada
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Martín-Campos
authors.forename: Lídia
authors.initials: L
authors.lastname: Cedó
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
mesh_terms: D000743:Anemia, Hemolytic / Q000209:etiology; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D001384:Azetidines / Q000627:therapeutic use; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D007410:Intestinal Diseases / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D051379:Mice; D010840:Phytosterols / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000209:etiology; D014973:Xanthomatosis / Q000209:etiology
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D010840:Phytosterols; D000069438:Ezetimibe