A case of ezetimibe-effective hypercholesterolemia with a novel heterozygous variant in ABCG5
| Autor: | Yujiro Nakano, Kumiko Shiba, Koh-ichiro Yoshiura, Kenji Ikeda, Kazutaka Tsujimoto, Yoshihiro Ogawa, Hitomi Shimizu, Hiroyuki Mishima, Chikara Komiya, Sumito Dateki, Tetsuya Yamada, Kenichi Kashimada |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
business.industry Endocrinology Diabetes and Metabolism PCSK9 030209 endocrinology & metabolism Familial hypercholesterolemia ABCG8 Gene mutation Compound heterozygosity medicine.disease 03 medical and health sciences 0302 clinical medicine Endocrinology Ezetimibe 030220 oncology & carcinogenesis Internal medicine LDL receptor medicine lipids (amino acids peptides and proteins) business Sitosterolemia medicine.drug |
| Zdroj: | Endocrine Journal. 67:1099-1105 |
| ISSN: | 1348-4540 0918-8959 |
| DOI: | 10.1507/endocrj.ej20-0044 |
| Popis: | Sitosterolemia is caused by homozygous or compound heterozygous gene mutations in either ATP-binding cassette subfamily G member 5 (ABCG5) or 8 (ABCG8). Since ABCG5 and ABCG8 play pivotal roles in the excretion of neutral sterols into feces and bile, patients with sitosterolemia present elevated levels of serum plant sterols and in some cases also hypercholesterolemia. A 48-year-old woman was referred to our hospital for hypercholesterolemia. She had been misdiagnosed with familial hypercholesterolemia at the age of 20 and her serum low-density lipoprotein cholesterol (LDL-C) levels had remained about 200-300 mg/dL at the former clinic. Although the treatment of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors was ineffective, her serum LDL-C levels were normalized by ezetimibe, a cholesterol transporter inhibitor. We noticed that her serum sitosterol and campesterol levels were relatively high. Targeted analysis sequencing identified a novel heterozygous ABCG5 variant (c.203A>T; p.Ile68Asn) in the patient, whereas no mutations were found in low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), or Niemann-Pick C1-like intracellular cholesterol transporter 1 (NPC1L1). While sitosterolemia is a rare disease, a recent study has reported that the incidence of loss-of-function mutation in the ABCG5 or ABCG8 gene is higher than we thought at 1 in 220 individuals. The present case suggests that serum plant sterol levels should be examined and ezetimibe treatment should be considered in patients with hypercholesterolemia who are resistant to HMG-CoA reductase inhibitors. |
| Databáze: | OpenAIRE |
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