Background: Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder presenting as isolated direct hyperbilirubinemia.DJS is rarely diagnosed in the neonatal period. The purpose of this study was to clarify the clinical features of neonatal DJS and to analyze the genetic mutation of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2). Methods: From 2013 to 2018, 135 infants with neonatal cholestasis at Seoul National University Hospital were enrolled. Genetic analysis was performed by neonatal cholestasis gene panel. To clarify the characteristics of neonatal DJS, the clinical and laboratory results of 6 DJS infants and 129 infants with neonatal cholestasis from other causes were compared. Results: A total of 8 different ABCC2 variants were identified among the 12 alleles of DJS. The most common variant was p.Arg768Trp (33.4%), followed by p.Arg100Ter (16.8%). Three novel variants were identified (p.Gly693Glu, p.Thr394Arg, and p.Asn718Ser). Aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in infants with DJS than in infants with neonatal cholestasis from other causes. Direct bilirubin and total bilirubin were significantly higher in the infants with DJS. Conclusions: We found three novel variants in 6 Korean infants with DJS. When AST and ALT levels are normal in infants with neonatal cholestasis, genetic analysis of ABCC2 permits an accurate diagnosis.

Background: Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder presenting as isolated direct hyperbilirubinemia.DJS is rarely diagnosed in the neonatal period. The purpose of this study was to clarify the clinical features of neonatal DJS and to analyze the genetic mutation of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2).Methods: From 2013 to 2018, 135 infants with neonatal cholestasis at Seoul National University Hospital were enrolled. Genetic analysis was performed by neonatal cholestasis gene panel. To clarify the characteristics of neonatal DJS, the clinical and laboratory results of 6 DJS infants and 129 infants with neonatal cholestasis from other causes were compared.Results: A total of 8 different ABCC2 variants were identified among the 12 alleles of DJS. The most common variant was p.Arg768Trp (33.4%), followed by p.Arg100Ter (16.8%). Three novel variants were identified (p.Gly693Glu, p.Thr394Arg, and p.Asn718Ser). Aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in infants with DJS than in infants with neonatal cholestasis from other causes. Direct bilirubin and total bilirubin were significantly higher in the infants with DJS.Conclusions: We found three novel variants in 6 Korean infants with DJS. When AST and ALT levels are normal in infants with neonatal cholestasis, genetic analysis of ABCC2 permits an accurate diagnosis.

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Hepatopulmonary syndrome (HPS) is defined as three distinct features: liver disease, hypoxemia, and intrapulmonary vasodilation. The purpose of this study was to investigate the clinical outcomes of pediatric HPS and to identify the risk factors for HPS in children with biliary atresia (BA). We performed a retrospective cohort study of all children who were diagnosed with HPS between 2000 and 2018 at Seoul National University Hospital. The clinical features and outcomes of the 10 patients diagnosed with HPS were reviewed. To clarify the risk factors of HPS in patients with BA, we reviewed 120 patients diagnosed with BA. Underlying liver disease was BA in 8 patients, portal vein agenesis in 1 patient, and portal vein thrombosis in 1 patient. A total of 7 patients underwent liver transplantation (LT). Currently, all seven patients, including 3 patients with severe HPS, survived after LT. The prevalence of HPS in children with BA was 7%. Polysplenia/interrupted inferior vena was the only risk factor for HPS in BA patients in multivariate analysis. The Pediatric End-Stage Liver Disease score was not associated with the development of HPS. Children with severe HPS undergoing LT had excellent outcomes. Screening for HPS in children with BA is required regardless of the severity of liver diseases.