短暂性新生儿胆汁淤积中BSEP/ABCB11抑制的组织学证明：一例报告

Histological demonstration of BSEP/ABCB11 inhibition in transient neonatal cholestasis: a case report.

作者信息

Baghdasaryan Anna, Ofner-Ziegenfuß Lisa, Lackner Carolin, Fickert Peter, Resch Bernhard, Morris Nicholas Mark, Deutschmann Andrea

机构信息

Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/2, 8036, Graz, Austria.

Institute for Human Genetics, Medical University of Graz, Graz, Austria.

出版信息

BMC Pediatr. 2020 Jul 9;20(1):340. doi: 10.1186/s12887-020-02201-x.

DOI:10.1186/s12887-020-02201-x

PMID:32646411

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7346433/

Abstract

BACKGROUND

Idiopathic or transient neonatal cholestasis (TNC) represents a group of cholestatic disorders with unidentified origin and remains a diagnosis of exclusion. Dysfunction of hepatobiliary transporters mediating excretion of biliary constituents from hepatocytes may play a central role in the pathogenesis of cholestasis. Despite variants of bile salt (BS) export pump (BSEP/ABCB11) have already been described in TNC, the pathogenic role of BSEP dysfunction in TNC remained so far elusive.

CASE PRESENTATION

We report on a newly-identified heterozygous ABCB11 missense variant (c.1345G > A, p.Glu449Lys) which was associated with prolonged cholestasis in a term infant after a complicated neonatal period. Moreover, we show for the first time almost completely abolished BSEP expression on the hepatocellular membrane in TNC.

CONCLUSION

This report demonstrates for the first time a close association between the prolonged cholestasis in infancy and impaired BSEP expression on the hepatocyte canalicular membrane in a heterozygous carrier of newly-identified ABCB11 variant.

摘要

背景

特发性或短暂性新生儿胆汁淤积症（TNC）是一组病因不明的胆汁淤积性疾病，目前仍为排除性诊断。介导胆汁成分从肝细胞排泄的肝胆转运体功能障碍可能在胆汁淤积的发病机制中起核心作用。尽管已在TNC中描述了胆汁盐（BS）输出泵（BSEP/ABCB11）的变体，但迄今为止，BSEP功能障碍在TNC中的致病作用仍不清楚。