title: A case of sitosterolemia due to compound heterozygous mutations inABCG5: clinical features and treatment outcomes obtained with colestimide and ezetimibe.
abstract: Sitosterolemia is a rare, autosomal recessively inherited disorder of lipid metabolism caused by mutations in the "ATP-binding cassette, subfamily G" member 5 and 8 proteins (encoded by theABCG5andABCG8genes, respectively), which play critical roles in the intestinal and biliary excretion of plant sterols. We report the clinical features and treatment outcomes of an 18-month-old Japanese girl with sitosterolemia, who presented with multiple linear and intertriginous xanthomas around the joint areas. Serum lipid analyses revealed elevated levels of total cholesterol (T-Chol: 866 mg/dL), low density lipoprotein-cholesterol (LDL-C: 679 mg/dL), and plant sterols (sitosterol: 24.6 mg/dL, campesterol: 19.2 mg/dL, stigmasterol: 1.8 mg/dL). Compound heterozygous mutations (p.R419H and p.R389H) were identified inABCG5. The patient was placed on a low cholesterol/low plant sterol diet and treated with colestimide (a bile acid sequestrant) and ezetimibe (an NPC1L1 inhibitor). Serum T-Chol and LDL-C levels decreased to normal within 2 mo, and plant sterol levels decreased by 30% within 4 mo. The xanthomas regressed gradually, and almost completely disappeared after 1.5 yr of treatment. No further reductions of plant sterol levels were observed. Long-term follow-up is important to verify appropriate therapeutic goals to prevent premature atherosclerosis and coronary artery disease.
authors.affiliation: Department of Pediatrics, Kawasaki Medical School, Okayama, Japan.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Pediatrics, Kawasaki Medical School, Okayama, Japan; Department of Pathophysiology and Metabolism, Kawasaki Medical School, Okayama, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuda
authors.affiliation: Department of Pediatrics, Kawasaki Medical School, Okayama, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Dermatology, Kawasaki Medical School, Okayama, Japan.
authors.forename: Takenobu
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Dermatology, Kawasaki Medical School, Okayama, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujimoto
authors.affiliation: Department of Pediatrics, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Pediatrics, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Dateki
authors.affiliation: Department of Pediatrics, Kawasaki Medical School, Okayama, Japan.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ouchi
keywords: ABCG5; colestimide; ezetimibe; sitosterolemia; xanthomas