Clinical and genetic features of sitosterolemia in Japan

Clin Chim Acta. 2022 May 1:530:39-44. doi: 10.1016/j.cca.2022.02.021. Epub 2022 Mar 4.

Abstract

Background and aim: Clinical manifestations and genetic backgrounds of Japanese patients with sitosterolemia have been unclear.

Materials and methods: We searched PubMed for studies using the keywords "sitosterolemia" or "phytosterolemia" and "Japan". Moreover, we added information from the members of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare (MHLW) of Japan.

Results: We identified 36 patients with sitosterolemia caused by biallelic pathogenic mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) or ATP-binding cassette subfamily G member 8 (ABCG8) from 31 families in Japan. The diagnosed age ranged from 0 to 64 years (median 13 years). The median sitosterol and LDL cholesterol levels were 100 μg/ml (IQR: 50-183), and 193 mg/dl (IQR: 108-295), respectively. All the patients exhibited cutaneous and/or tendon xanthomas, up to 9 (25%) patients exhibited premature coronary artery disease, 5 (16%) patients exhibited arthritis, and 8 (22%) patients exhibited blood abnormalities. Ezetimibe was administered to all the patients, including infantile cases, while statins, colestimide, evolocumab, probucol, and LDL apheresis were also used.

Conclusion: We are providing a demographic overview of the clinical and genetic backgrounds of Japanese patients with sitosterolemia.

Keywords: ABCG5; ABCG8; Familial hypercholesterolemia; Sitosterolemia.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 8 / genetics
  • Adenosine Triphosphate
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Humans
  • Hypercholesterolemia
  • Infant
  • Infant, Newborn
  • Intestinal Diseases* / diagnosis
  • Intestinal Diseases* / genetics
  • Intestinal Diseases* / pathology
  • Japan
  • Lipid Metabolism, Inborn Errors* / diagnosis
  • Lipid Metabolism, Inborn Errors* / genetics
  • Lipid Metabolism, Inborn Errors* / pathology
  • Middle Aged
  • Phytosterols* / adverse effects
  • Phytosterols* / genetics
  • Young Adult

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • Phytosterols
  • Adenosine Triphosphate

Supplementary concepts

  • Sitosterolemia