Wang HH, Wen FQ, Dai DL, Wang JS, Zhao J, Setchell KD, Shi LN, Zhou SM, Liu SX, Yang QH. Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature. World J Gastroenterol 2018; 24(35): 4086-4092 [PMID: 30254413 DOI: 10.3748/wjg.v24.i35.4086]
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Wang HH, Wen FQ, Dai DL, Wang JS, Zhao J, Setchell KD, Shi LN, Zhou SM, Liu SX, Yang QH. Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature. World J Gastroenterol 2018; 24(35): 4086-4092 [PMID: 30254413 DOI: 10.3748/wjg.v24.i35.4086]
World J Gastroenterol. Sep 21, 2018; 24(35): 4086-4092 Published online Sep 21, 2018. doi: 10.3748/wjg.v24.i35.4086
Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature
Jian-She Wang, Jing Zhao, Center for Pediatric Liver Diseases, Children’s Hospital of Fudan University, Shanghai 201102, China
Kenneth DR Setchell, Department of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, United States
Li-Na Shi, MyGenostics Incorporation, Konggang Industrial Park, Beijing 101318, China
Author contributions: Wang HH drafted the manuscript and analyzed the data; Wen FQ, Wang JS and Zhao J contributed to sample analysis and patients’ treatment regimens; Setchell KD contributed to the analysis, interpretation of urinary bile acids and finalized the manuscript; Wang HH, Dai DL, Zhou SM, Liu SX and Yang QH were involved in patient management and follow-up; Shi LN performed gene sequencing and analysis; Dai DL conceived and supervised the study; Wang HH and Wen FQ contributed equally to this work. All of the authors approved submission.
Supported bythe Guangdong Medical Research Foundation, No. A2018550.
Informed consent statement: Consent was obtained from the parents of the patient for publication of the case report and any accompanying images.
Conflict-of-interest statement: The authors who took part in this study declare that they do not have anything to disclose regarding funding or a conflict of interest with respect to this manuscript. Setchell KD is a consultant to Retrophin and has minor equity in Asklepion Pharmaceuticals.
Received: June 7, 2018 Peer-review started: June 7, 2018 First decision: June 20, 2018 Revised: July 17, 2018 Accepted: August 1, 2018 Article in press: August 1, 2018 Published online: September 21, 2018 Processing time: 105 Days and 20.1 Hours
ARTICLE HIGHLIGHTS
Case characteristics
A 2 mo old male infant presented with hyperbilirubinemia and coagulopathy, but normal bile acid and γ-glutamyltransferase.
Clinical diagnosis
Infant cholestatic liver disease, diagnosed by elevated direct bilirubin and alanine aminotransferase.
Differential diagnosis
Virus hepatitis, congenital bile duct dysplasia, genetic metabolic diseases, and autoimmune hepatitis.
Laboratory diagnosis
Hyperbilirubinemia, coagulopathy, and impaired liver function.
Treatment
The patient was initially given ursodeoxycholic acid (UDCA) treatment. We changed UDCA to chenodeoxycholic acid (CDCA) (80 mg/d) after one week of ineffective UCDA treatment. After two months of oral CDCA treatment, urine bile acid analyses indicated that the CDCA dose of 80 mg/d was insufficient to complete the suppression of atypical bile acids. We thus increased the dose of CDCA to 100 mg/d, which proved adequate to down-regulate hepatic bile acid synthesis based on the second urine bile acid analyses.
Related reports
More than 20 cases of primary 5β-reductase deficiency have been reported, and over ten variant mutations in the aldo-ketoreductase family 1 member D1 (AKR1D1) gene are attributed to a defect in 5β-reductase.
Term explanation
Aldo-ketoreductase family 1 member D1 (AKR1D1) encodes Δ4-3-oxosteroid 5β-reductase; its deficiency results in a lack of primary bile acids and increased synthesis of 3-oxo-Δ4 bile and allo-bile acids.
Experiences and lessons
Gene analysis is essential for the accurate diagnosis of primary 3-oxo-Δ4-steroid 5β-reductase deficiency. Early diagnosis and adequate supplementation with CDCA are vital for the amelioration of clinical symptoms.
