Case Report
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Hui-Hui Wang, Fei-Qiu Wen, Dong-Ling Dai, Jian-She Wang, Jing Zhao, Kenneth DR Setchell, Li-Na Shi, Shao-Ming Zhou, Si-Xi Liu, Qing-Hua Yang
Hui-Hui Wang, Fei-Qiu Wen, Dong-Ling Dai, Shao-Ming Zhou, Si-Xi Liu, Qing-Hua Yang, Gastroenterology Department, Shenzhen Children’s Hospital, Shenzhen 518036, Guangdong Province, China
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 by the 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.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dong-Ling Dai, MD, PhD, Chief Doctor, Gastroenterology Department, Shenzhen Children’s Hospital, 7019 Yitian Road, Futian District, Shenzhen 518036, Guangdong Province, China.
Telephone: +86-755-83008333 Fax: +86-755-83008333
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
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.


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.