Novel ABCC2 mutations in a neonate with Dubin-Johnson syndrome: a case report

Abstract

Background Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder caused by mutations in the ABCC2 gene, leading to impaired excretion of conjugated bilirubin. Neonatal or infantile onset is uncommon and easily misdiagnosed as biliary atresia or progressive familial intrahepatic cholestasis. Case presentation We report a female infant who presented with persistent jaundice since birth (onset in the neonatal period, ≤28 days). A definitive genetic diagnosis of Dubin-Johnson syndrome (DJS) was established at 11 months of age through next-generation sequencing. Her subsequent 5-year follow-up indicates a favorable clinical course. Laboratory tests revealed consistently normal transaminase levels with elevated total bilirubin (peak 120.3 μmol/L at 52 days), direct bilirubin (peak 61.3 μmol/L), and gamma-glutamyl transferase (88 U/L). Next-generation sequencing identified two novel compound heterozygous mutations in the ABCC2 gene: c.2443C>T (p.R815X, nonsense) inherited from the mother and c.4465_4473delinsGGCCCACAG (p.1489_1491delinsGPQ, in-frame) inherited from the father. Both mutations were classified as pathogenic/likely pathogenic according to ACMG guidelines (c.2443C>T: PVS1, PM2, PM3; c.4465_4473delinsGGCCCACAG: PM2, PM3, PM4) and have not been previously reported. Ursodeoxycholic acid therapy was administered, and bilirubin levels showed progressive decline over time; however, this improvement may also reflect the spontaneous trend toward resolution that is characteristic of the natural history of DJS. Conclusion This case expands the mutational spectrum of ABCC2 gene and highlights the critical role of genetic testing in early diagnosis of infantile DJS, thereby avoiding unnecessary invasive procedures. The favorable prognosis with conservative management further supports the benign nature of this condition.