Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan

Togawa, Takao; Mizuochi, Tatsuki; Sugiura, Tetsuro; Kusano, Hironori; Tanikawa, Ken; Sasaki, Takato; Ichinose, Fumio; Kagimoto, Seiichi; Tainaka, Takahisa; Uchida, Hiroo; Saitoh, Shinji

doi:10.1016/j.jpeds.2017.12.058

Cited by 39 publications

(60 citation statements)

References 26 publications

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“…A total of 135 patients were enrolled, 6 of whom were diagnosed with neonatal DJS. We defined neonatal cholestasis as serum direct bilirubin level (DB) greater than 1.0 mg/dL when serum total bilirubin (TB) was ≤ 5.0 mg/dL or a serum DB level greater than 20% of serum TB when serum TB was > 5.0 mg/dL [5,6]. Initial clinical symptoms, laboratory results, liver biopsy findings, and ABCC2 genetic mutations were reviewed.…”

Section: Comparison Of Subjects With Other Infants With Neonatal Cholmentioning

confidence: 99%

Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

Kim

Seong

et al. 2020

BMC Pediatr

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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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Section: Comparison Of Subjects With Other Infants With Neonatal Cholmentioning

confidence: 99%

Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

Kim

Seong

et al. 2020

BMC Pediatr

View full text Add to dashboard Cite

show abstract

“…A total of 135 patients were enrolled, 6 of whom were diagnosed with neonatal DJS. We de ned neonatal cholestasis as serum direct bilirubin level (DB) greater than 1.0 mg/dL when serum total bilirubin (TB) was ≤ 5.0 mg/dL or a serum DB level greater than 20% of serum TB when serum TB was > 5.0 mg/dL [5,6]. Initial clinical symptoms, laboratory results, liver biopsy ndings, and ABCC2 genetic mutations were reviewed.…”

Section: Comparison Of Subjects With Other Infants With Neonatal Cholmentioning

confidence: 99%

Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

Kim

Seong

et al. 2020

Preprint

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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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“…There is also increased urinary excretion of coproporphyrin I and macroscopic hepatic lysosomal black pigment accumulation. 1 Genetic testing in our patient, with parallel panel sequencing for genetic forms of cholestasis, demonstrated 2 novel heterozygous pathogenic mutations of ABCC2 associated with loss of function. The first mutation was a nonsense (c.1627C>T) variant, which introduced a premature stop codon at codon 543 [p.(Gln543*)] in exon 12, resulting in either production of a truncated protein (shortened by 1002 amino acid residues) or nonsense-mediated messenger RNA decay.…”

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confidence: 77%

A Rare Cause of Neonatal Cholestasis Without Liver Dysfunction

2019

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An 8-week-old girl presented for investigation of a conjugated hyperbilirubinemia. She was born at term, breastfed with supplemental bottle top ups. Her stool was acholic and she was the second child born to healthy, nonconsanguinous Vietnamese migrant parents. She had been well with no recent illnesses and was not taking any medications. On examination she looked well, with no dysmorphic features and was deeply jaundiced with a soft liver edge palpable 3 cm below the right costal margin. There was no palpable splenomegaly. Her liver function tests demonstrated a total bilirubin level of 382 mmol/L (reference range, <21 mmol/L), conjugated bilirubin 372 mmol/L (reference range, <5 mmol/L), serum albumin 41 g/L (reference range, 31-46 g/L

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Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan

Cited by 39 publications

References 26 publications

Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

A Rare Cause of Neonatal Cholestasis Without Liver Dysfunction

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