Baghdasaryan Anna, Ofner-Ziegenfuß Lisa, Lackner Carolin, Fickert Peter, Resch Bernhard, Morris Nicholas Mark, Deutschmann Andrea
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.
BMC Pediatr. 2020 Jul 9;20(1):340. doi: 10.1186/s12887-020-02201-x.
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.
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.
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.
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。
我们报告了一个新发现的杂合ABCB11错义变体（c.1345G＞A，p.Glu449Lys），该变体与一名足月儿在经历复杂的新生儿期后出现的胆汁淤积延长有关。此外，我们首次发现TNC患者肝细胞膜上的BSEP表达几乎完全缺失。
本报告首次证明，在新发现的ABCB11变体杂合携带者中，婴儿期胆汁淤积延长与肝小胆管膜上BSEP表达受损密切相关。
