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

Steroid 5β-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307 (p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid (UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid (CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.

Keywords: Aldo-keto reductase family 1 member D1, Cholestasis, Congenital bile acid synthesis defect, Gene mutation

Core tip: We report a case of an infant with primary 3-oxo-Δ4-steroid 5β-reductase deficiency with a novel missense mutation in the aldo-keto reductase family 1 member D1 (AKR1D1) gene. The patient was successfully treated by early adequate supplementation with chenodeoxycholic acid (CDCA). This case suggests that a novel compound heterozygous R307C mutation and loss of heterozygosity in the AKR1D1 gene play a pathogenic role in congenital bile acid synthesis defect type 2. Accurate diagnosis of the disease and early adequate supplementation with CDCA are vital for the amelioration of symptoms in clinical practice.