ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed
ABCB4 variants in adult patients with cholestatic disease are frequent and underdiagnosed
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DOI：
10.1016/j.dld.2020.12.003
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发表时间：
2021-02-22
影响因子：
4.5
通讯作者：
Beretta-Piccoli, Benedetta Terziroli
中科院分区：
文献类型：
--
作者：
Avena, Antonella;Puggelli, Sandro;Beretta-Piccoli, Benedetta Terziroli
背景：杂合子ABCB4变异体在胆汁淤积的成人中没有常规检测，因为它们的罕见性和高成本。方法：纳入19例出现不明原因胆汁淤积和/或复发性胆结石的成年患者；由于缺乏健康保险的批准，有5例没有进行基因分型。结果：在7名患者中发现杂合ABCB4变异，随后对12名家庭成员进行级联检测：1名患者在40岁时因终末期肝病接受了肝移植；一个患有代偿性肝硬化；所有有症状的成年人都有胆结石，包括4名低磷脂相关性胆石症患者；妊娠期肝内胆汁淤积4例；所有儿童和一名54岁女性均无症状。基因型：A和C家族：C . 2211g >A （p.Ala737=）与C . 959c >T （p.Ser320Phe）合并；B族：C . 1130t >C (p.c ile377thr)；家族D：大缺失去除ABCB4外显子1-4和ABCB1、RUNDC3B、SLC25A40、DBF4、ADAM22外显子1-3；E系列：C . 1565t >C (p.Phe522Ser)；F族：C .1356+2T>C与C . 217c >G结合（p.Leu73Val）。所有患者对熊去氧胆酸均有反应。结论：我们在我们中心就诊的半数不明原因胆汁淤积和/或复发性胆结石患者中发现了ABCB4变异，这表明这种疾病的诊断和治疗不足，不仅对患者及其家人造成了严重后果，而且在医疗保健费用方面也造成了严重后果。(C) 2020 Editrice gastroenteritaliana S.r.l, Elsevier Ltd.出版版权所有。
Background: Heterozygous ABCB4 variants are not routinely tested in adults with cholestasis because of their supposed rarity and high costs.Methods: Nineteen adult patients presenting with unexplained cholestasis, and/or recurrent gallstones were included; genotyping was not done in five due to lack of health insurance approval.Results: heterozygous ABCB4 variants were identified in seven patients, followed by cascade testing of 12 family members: one patient underwent liver transplantation at age 40 for end-stage liver disease; one had compensated cirrhosis; all symptomatic adults had gallstones, including four with low phospholipid-associated cholelithiasis; four had intrahepatic cholestasis of pregnancy; all children and one 54-year old female were asymptomatic. Genotype: Families A and C: c.2211G>A (p.Ala737=) combined with c.959C>T (p.Ser320Phe) in one subject; Family B: c.1130T>C (p.Ile377Thr); Family D: large deletion removing ABCB4 exons 1-4 plus ABCB1, RUNDC3B, SLC25A40, DBF4, ADAM22 exons 1-3; Family E: c.1565T>C (p.Phe522Ser); Family F: c.1356+2T>C combined with c.217C>G (p.Leu73Val). All patients responded to ursodeoxycholic acid.Conclusions: We found ABCB4 variants in half of the adults with unexplained cholestasis and/or recurrent gallstones presenting at our center, suggesting that this condition is underdiagnosed and undertreated, with serious consequences not only for the patients and their families, but also in terms of healthcare costs. (C) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.