A case of ezetimibe-effective hypercholesterolemia with a novel heterozygous variant in ABCG5
A case of ezetimibe-effective hypercholesterolemia with a novel heterozygous variant in ABCG5
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DOI：
10.1507/endocrj.ej20-0044
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发表时间：
2020-01-01
影响因子：
2
通讯作者：
Yamada, Tetsuya
中科院分区：
文献类型：
--
作者：
Nakano, Yujiro;Komiya, Chikara;Yamada, Tetsuya
谷甾醇血症是由ATP结合盒亚家族G成员5（ABCG 5）或8（ABCG 8）中的纯合或复合杂合基因突变引起的。由于ABCG 5和ABCG 8在中性固醇排泄到粪便和胆汁中起关键作用，因此谷甾醇血症患者的血清植物固醇水平升高，并且在某些情况下还存在高胆固醇血症。一位48岁的女性因高胆固醇血症被转诊到我院。她在20岁时被误诊为家族性高胆固醇血症，她的血清低密度脂蛋白胆固醇（LDL-C）水平在以前的诊所保持在200-300 mg/dL左右。尽管羟甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂治疗无效，但她的血清LDL-C水平通过依折麦布（一种胆固醇转运蛋白抑制剂）恢复正常。我们注意到她的血清谷甾醇和菜油甾醇水平相对较高。靶向分析测序确定了一种新的杂合ABCG 5变异体（c.203A>T; p.Ile68Asn），而在低密度脂蛋白受体（LDLR）、前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）或尼曼-匹克C1样细胞内胆固醇转运蛋白1（NPC 1 L1）中未发现突变。虽然谷甾醇血症是一种罕见的疾病，但最近的一项研究报告称，ABCG 5或ABCG 8基因功能丧失突变的发生率高于我们认为的1/220。本病例表明，应检查血清植物甾醇水平，并应考虑对HMG-CoA还原酶抑制剂耐药的高胆固醇血症患者进行依折麦布治疗。
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.