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A case of ezetimibe-effective hypercholesterolemia with a novel heterozygous variant in ABCG5.
- Source :
-
Endocrine journal [Endocr J] 2020 Nov 28; Vol. 67 (11), pp. 1099-1105. Date of Electronic Publication: 2020 Jul 09. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Cholesterol analogs & derivatives
Cholesterol blood
Cholesterol, LDL blood
Diagnostic Errors
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Hypercholesterolemia diagnosis
Hypercholesterolemia genetics
Hyperlipoproteinemia Type II diagnosis
Intestinal Diseases diagnosis
Intestinal Diseases genetics
Lipid Metabolism, Inborn Errors diagnosis
Lipid Metabolism, Inborn Errors genetics
Loss of Function Mutation
Middle Aged
Phytosterols blood
Phytosterols genetics
Sitosterols blood
Treatment Failure
ATP Binding Cassette Transporter, Subfamily G, Member 5 genetics
Anticholesteremic Agents therapeutic use
Ezetimibe therapeutic use
Hypercholesterolemia drug therapy
Intestinal Diseases drug therapy
Lipid Metabolism, Inborn Errors drug therapy
Lipoproteins genetics
Phytosterols adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1348-4540
- Volume :
- 67
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Endocrine journal
- Publication Type :
- Academic Journal
- Accession number :
- 32641618
- Full Text :
- https://doi.org/10.1507/endocrj.EJ20-0044