Takao Togawa1, Tatsuki Mizuochi2, Tokio Sugiura1, Hironori Kusano3, Ken Tanikawa3, Takato Sasaki4, Fumio Ichinose5, Seiichi Kagimoto6, Takahisa Tainaka7, Hiroo Uchida7, Shinji Saitoh1. 1. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 2. Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan. Electronic address: mizuochi_tatsuki@kurume-u.ac.jp. 3. Department of Pathology, Kurume University School of Medicine, Kurume, Japan. 4. Department of Pediatric Surgery, Ibaraki Children's Hospital, Ibaraki, Japan. 5. Department of Pediatrics, Saga Medical Center Koseikan, Saga, Japan. 6. Division of General Pediatrics, Saitama Children's Medical Center, Saitama, Japan. 7. Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Abstract
OBJECTIVE: To clarify the clinical, pathologic, and genetic features of neonatal Dubin-Johnson syndrome. STUDY DESIGN: Ten patients with neonatal Dubin-Johnson syndrome were recruited from 6 pediatric centers in Japan between September 2013 and October 2016. Clinical and laboratory course, macroscopic and microscopic liver findings, and molecular genetic findings concerning ATP-binding cassette subfamily C member 2 (ABCC2) were retrospectively and prospectively examined. RESULTS: All neonates exhibited cholestasis, evident as prolonged jaundice with or without acholic stools and elevations of serum direct bilirubin as well as γ-glutamyltransferase or total bile acids. Only 38% (3 of 8) of patients who underwent liver biopsy showed a grossly black liver or melanin-like pigment deposits in hepatocytes; their biopsies were performed in early infancy. Immunohistochemically, all liver specimens showed no expression of multidrug resistance-associated protein 2 but increased expression of the bile salt export pump protein. Homozygous or compound heterozygous pathogenic variants of ABCC2 were identified in all patients, representing 11 distinct pathogenic variants including 2 not previously reported. CONCLUSIONS: Immunohistochemical staining of the liver for multidrug resistance-associated protein 2 and molecular genetic analysis of ABCC2 are crucial for accurate diagnosis of neonatal Dubin-Johnson syndrome.
OBJECTIVE: To clarify the clinical, pathologic, and genetic features of neonatal Dubin-Johnson syndrome. STUDY DESIGN: Ten patients with neonatal Dubin-Johnson syndrome were recruited from 6 pediatric centers in Japan between September 2013 and October 2016. Clinical and laboratory course, macroscopic and microscopic liver findings, and molecular genetic findings concerning ATP-binding cassette subfamily C member 2 (ABCC2) were retrospectively and prospectively examined. RESULTS: All neonates exhibited cholestasis, evident as prolonged jaundice with or without acholic stools and elevations of serum direct bilirubin as well as γ-glutamyltransferase or total bile acids. Only 38% (3 of 8) of patients who underwent liver biopsy showed a grossly black liver or melanin-like pigment deposits in hepatocytes; their biopsies were performed in early infancy. Immunohistochemically, all liver specimens showed no expression of multidrug resistance-associated protein 2 but increased expression of the bile salt export pump protein. Homozygous or compound heterozygous pathogenic variants of ABCC2 were identified in all patients, representing 11 distinct pathogenic variants including 2 not previously reported. CONCLUSIONS: Immunohistochemical staining of the liver for multidrug resistance-associated protein 2 and molecular genetic analysis of ABCC2 are crucial for accurate diagnosis of neonatal Dubin-Johnson syndrome.
Authors: Fatemeh Alaei Faradonbeh; Hana Lastuvkova; Jolana Cermanova; Milos Hroch; Zuzana Nova; Martin Uher; Petra Hirsova; Petr Pavek; Stanislav Micuda Journal: Front Physiol Date: 2022-03-21 Impact factor: 4.755