title: Current therapy for patients with sitosterolemia--effect of ezetimibe on plant sterol metabolism.
abstract: Sitosterolemia is a rare, autosomal recessive inherited sterol storage disease associated with high tissue and serum plant sterol concentrations, caused by mutations in the adenosine triphosphate-bind-ing cassette (ABC) transporter ABCG5 or ABCG8 genes. Markedly increased serum concentration of plant sterols. such as sitosterol and campesterol, cause premature atherosclerosis and massive xanthomas. Hitherto known treatments for sitosterolemia, including a low-sterol diet, bile-salt binding resins, ileal bypass surgery and low density lipoprotein (LDL) apheresis have not yielded sufficient reduction of serum plant sterol levels and many patients show a sustained elevation of plant sterol levels, subsequently developing premature atherosclerotic cardiovascular diseases. Ezetimibe, an inhibitor of intestinal cholesterol absorption through its binding to Niemann-Pick C1-like 1 (NPC1L1), has been widely used for decreasing serum LDL-cholesterol levels in patients with hypercholesterolemia. Ezetimibe also reduces the gastrointestinal absorption of plant sterols, thereby also lowering the serum concentrations of plant sterols. This pharmacological property of ezetimibe shows its potential as a novel effective therapy for sitosterolemia. In the current review, we discuss the current therapy for patients with sitosterolemia and present two Japanese adolescent patients with this disease, one of whom underwent percutaneous coronary intervention for accelerated coronary atherosclerosis. Ezetimibe administration in addition to conventional drug therapy successfully reduced serum sitosterol levels by 51.3% and 48.9%, respectively, in the two patients, demonstrating ezetimibe as a novel and potent treatment agent for sitosterolemia that could work additively with conventional drug therapy.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tsubakio-Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakagawa-Toyama
authors.forename: Daisaku
authors.initials: D
authors.lastname: Masuda
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohama
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007082:Ileum / Q000601:surgery; D007475:Ion Exchange Resins / Q000627:therapeutic use; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000628:therapy; D008074:Lipoproteins / Q000235:genetics; D008297:Male; D008954:Models, Biological; D020125:Mutation, Missense; D010840:Phytosterols / Q000378:metabolism*; D012855:Sitosterols / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D001384:Azetidines; D001647:Bile Acids and Salts; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007475:Ion Exchange Resins; D008074:Lipoproteins; D010840:Phytosterols; D012855:Sitosterols; C025473:gamma-sitosterol; C021255:stigmastanol; D000069438:Ezetimibe