A case of sitosterolemia due to compound heterozygous mutations in <i>ABCG5</i>: clinical features and treatment outcomes obtained with colestimide and ezetimibe

• Ono Sahoko

  Department of Pediatrics, Kawasaki Medical School, Okayama, Japan

• Matsuda Junko

  Department of Pediatrics, Kawasaki Medical School, Okayama, Japan Department of Pathophysiology and Metabolism, Kawasaki Medical School, Okayama, Japan

• Saito Aki

  Department of Pediatrics, Kawasaki Medical School, Okayama, Japan

• Yamamoto Takenobu

  Department of Dermatology, Kawasaki Medical School, Okayama, Japan

• Fujimoto Wataru

  Department of Dermatology, Kawasaki Medical School, Okayama, Japan

• Shimizu Hitomi

  Department of Pediatrics, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan

• Dateki Sumito

  Department of Pediatrics, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki, Japan

• Ouchi Kazunobu

  Department of Pediatrics, Kawasaki Medical School, Okayama, Japan

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 the ABCG5 and ABCG8 genes, 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 in ABCG5. 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.

Journal

• Clinical Pediatric Endocrinology

  Clinical Pediatric Endocrinology 26 (1), 17-23, 2017

  The Japanese Society for Pediatric Endocrinology

Keywords

• sitosterolemia
• xanthomas
• ABCG5
• colestimide
• ezetimibe

Details

• CRID: 1390282679459298816
• NII Article ID: 130005308194
• DOI: 10.1297/cpe.26.17
• ISSN: 13477358
• ISSN: 09185739
• Web Site: https://www.jstage.jst.go.jp/article/cpe/26/1/26_2016-0024/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017307891
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed