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Abstract Details
Progressive familial intrahepatic cholestasis - farnesoid X receptor deficiency due to NR1H4mutation: A case report
World J Clin Cases. 2021 May 26;9(15):3631-3636.doi: 10.12998/wjcc.v9.i15.3631.
Piotr Czubkowski1, Richard J Thompson2, Irena Jankowska3, A S Knisely4, Milton Finegold5, Pamela Parsons5, Joanna Cielecka-Kuszyk6, Sandra Strautnieks2, Joanna Pawlowska3, Laura N Bull7
Author information
1Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw 04-730, Poland. p.czubkowski@ipczd.pl.
2Institute of Liver Studies, King's College London Hospital, London SE5 9RS, United Kingdom.
3Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw 04-730, Poland.
4Institut für Pathologie, Medizinische Universität Graz, Graz 8010, Austria.
5Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, United States.
6Department of Pathology, The Children's Memorial Health Institute, Warsaw 04-730, Poland.
7Department of Medicine and Institute for Human Genetics, UCSF Liver Center Laboratory, University of California San Francisco, San Francisco, CA 94143, United States.
Abstract
Background: Functioning farnesoid X receptor (FXR; encoded by NR1H4) is key to normal bile acid homeostasis. Biallelic mutations in NR1H4 are reported in a few children with intrahepatic cholestasis. We describe a boy with progressive familial intrahepatic cholestasis and homozygous mutation in NR1H4.
Case summary: A boy had severe neonatal cholestasis with moderate hypercholanemia and persistently elevated alpha-fetoprotein. Despite medical treatment, coagulopathy was uncontrollable, prompting liver transplantation at age 8 mo with incidental splenectomy. The patient experienced catch-up growth with good liver function and did not develop allograft steatosis. However, 1 year after transplant, he died from an acute infection, considered secondary to immunosuppression and asplenia. A homozygous protein-truncating mutation, c.547C > T, p.(Arg183Ter), was subsequently identified in NR1H4, and both parents were shown to be heterozygous carriers. Absence of FXR and of bile salt export pump expression was confirmed by immunostaining of explanted liver.
Conclusion: Severe cholestasis with persistently high alpha-fetoprotein and modest elevation of serum bile acid levels may suggest FXR deficiency. Some patients with FXR deficiency may not develop allograft steatosis and may respond well to liver transplantation.