Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 26, 2021; 9(15): 3631-3636
Published online May 26, 2021. doi: 10.12998/wjcc.v9.i15.3631
Progressive familial intrahepatic cholestasis — farnesoid X receptor deficiency due to NR1H4 mutation: A case report
Piotr Czubkowski, Richard J Thompson, Irena Jankowska, A S Knisely, Milton Finegold, Pamela Parsons, Joanna Cielecka-Kuszyk, Sandra Strautnieks, Joanna Pawłowska, Laura N Bull
Piotr Czubkowski, Irena Jankowska, Joanna Pawłowska, Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
Richard J Thompson, Sandra Strautnieks, Institute of Liver Studies, King's College London Hospital, London SE5 9RS, United Kingdom
A S Knisely, Institut für Pathologie, Medizinische Universität Graz, Graz 8010, Austria
Milton Finegold, Pamela Parsons, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, United States
Pamela Parsons, Texas Children’s Hospital, Houston, TX 77030, United States
Joanna Cielecka-Kuszyk, Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
Laura N Bull, Department of Medicine and Institute for Human Genetics, UCSF Liver Center Laboratory, University of California San Francisco, San Francisco, CA 94143, United States
Author contributions: All authors contributed significantly to the preparation of the manuscript; Czubkowski P, Bull LN, Thompson RJ, Knisely AS, Jankowska I and Pawłowska J contributed to conception and design of the case presentation, acquisition of data and case description; Bull LN, Strautnieks S and Thompson RJ contributed to genetic studies; Knisely AS, Finegold M, Parsons P and Cielecka-Kuszyk J contributed to histopathological assessment; Czubkowski P, Bull LN, Thompson RJ and Knisely AS contributed to drafting the article and making critical revisions related to the content of the manuscript; All authors have read and approve the final manuscript.
Supported by National Institutes of Health, No. R01DK094828; and National Human Genome Research Institute, No. UM1 HG006493 and No. U24 HG008956.
Informed consent statement: Parental consent was obtained for hospitalizations and all the procedures described in the manuscript.
Conflict-of-interest statement: Dr. Thompson consults for Albireo, Mirum, GenerationBio, Alnylam, Qing Bile, Horizon, Sana, and Retrophin and has share options in Qing Bile and GenerationBio. Other authors report no conflicts of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016) and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Piotr Czubkowski, MD, PhD, Associate Professor, Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, Warsaw 04-730, Poland. p.czubkowski@ipczd.pl
Received: October 17, 2020
Peer-review started: October 17, 2020
First decision: November 3, 2020
Revised: December 16, 2020
Accepted: February 24, 2021
Article in press: February 24, 2021
Published online: May 26, 2021
Core Tip

Core Tip: Despite the central role farnesoid X receptor (FXR) plays in bile acid metabolism, only a few children with cholestasis and biallelic FXR deficiency have been reported, and that only recently. Using banked DNA from patients without previous successful genetic diagnosis, we have identified a child with a homozygous mutation predicted to truncate FXR prematurely. We describe his disease course before and after liver transplantation, accompanied by immunohistochemical studies. This report adds meaningfully to the available information regarding disease course and outcomes in patients with severe FXR deficiency. It highlights biochemical findings that may be characteristic of FXR deficiency.