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

• 主要な著者: Anna Baghdasaryan (著者), Lisa Ofner-Ziegenfuß (著者), Carolin Lackner (著者), Peter Fickert (著者), Bernhard Resch (著者), Nicholas Mark Morris (著者), Andrea Deutschmann (著者)
• フォーマット: 図書
• 出版事項: BMC, 2020-07-01T00:00:00Z.
• 主題: article
• オンライン･アクセス: Connect to this object online.
• Notes: 10.1186/s12887-020-02201-x; 1471-2431
• Keywords: BSEP deficiency; Transient neonatal cholestasis; Pediatrics; RJ1-570
• Source: BMC Pediatrics, Vol 20, Iss 1, Pp 1-5 (2020)

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.