A boy exhibiting conjugated hyperbilirubinemia from birth, with elevated serum gamma-glutamyl transpeptidase activity (GGT), developed liver failure unusually early (7mo); GGT concomitantly normalized. ABCB4 disease was suspected, but no ABCB4 lesion was found. The boy was instead homozygous for ABCB11 variant c.1213 T>C (p.(Cys405Arg)), which is predicted to affect protein function. Both ABCB4 and ABCB11 were normally expressed in the explanted liver, with intralobular cholestasis; however, large-duct sclerosing cholangiopathy and ductal-plate malformation also were present. The primary-cilium constituent doublecortin domain containing 2 (DCDC2) was not expressed. Co-existence of ABCB11 disease and DCDC2 disease was proposed. Further testing identified homozygosity for the canonical-receptor splice-site variant c.294-2A>G (p.?) in DCDC2. Our report emphasizes the need to integrate clinical, histological, and genetic data in patients with neonatal cholestasis.

出生时表现出共轭高胆红素血症的男孩，血清γ-谷氨酰转肽酶活性（GGT）升高，异常地发展为肝衰竭（7mo）。GGT同时标准化。怀疑有ABCB4病，但未发现ABCB4病灶。这个男孩是ABCB11变体c.1213 T> C（p。（Cys405Arg））的纯合子，据预测会影响蛋白质功能。ABCB4和ABCB11均在外植肝脏中正常表达，并伴有小叶内胆汁淤积。然而，也存在大血管硬化性胆管病和导管板畸形。没有表达包含2的初级纤毛成分双皮质素域（DCDC2）。ABCB11疾病与DCDC2并存提出了疾病。进一步的测试确定了DCDC2中典型受体剪接位点变异体c.294-2A> G（p。？）的纯合性。我们的报告强调需要整合新生儿胆汁淤积患者的临床，组织学和遗传数据。