Literature review and report of three cases of Dubin-Johnson syndrome related to ABCC2 gene mutations in children.

Objective: The aim of the present study was to analyze the clinical features of Dubin-Johnson syndrome (DJS) related to ABCC2 gene mutations in children and to review the relevant literature to improve understanding of this type of genetic disease and reduce misdiagnosis.

Methods: Three children with clinically suspected DJS who were treated at Beijing Children's Hospital of Capital Medical University between 2017 and 2020 were enrolled in the study. The target genes were captured and sequenced using GenCap target gene capture technology and a new generation of high-throughput sequencing technology (Beijing Mykino Company). The clinical and genetic characteristics were analyzed and summarized.

Results: Two of the cases were female and one was male. All three cases were in early infancy and in good general health. Case 1 was complicated with unilateral hypertrophy, Case 2 was complicated with pneumonia, anemia, myocardial injury, and bilateral inguinal hernia, and Case 3 was complicated with patent foramen ovale and a ventricular septal defect. In all three cases, total bilirubin was elevated, with the main increase being in direct bilirubin (DBIL) and varying degrees of elevated alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), and total bile (TBA). Genetic testing indicated that there were seven gene mutations in ABCC2, two mutation sites of which had not been reported previously.

Conclusion: The clinical manifestations of DJS are non-specific and are mainly characterized by elevated DBIL. Some children might have different degrees of hepatic function abnormality and cholestasis. Due to the lack of serological markers, the diagnosis of DJS is difficult, but genetic testing, along with the formation of pedigree analysis and verification, could be used for accurate diagnosis. Novel mutations might enrich the spectrum of ABCC2 gene mutation.