Case Report
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2015; 21(8): 2550-2557
Published online Feb 28, 2015. doi: 10.3748/wjg.v21.i8.2550
Hepatic phenotypes of HNF1B gene mutations: A case of neonatal cholestasis requiring portoenterostomy and literature review
Radana Kotalova, Petra Dusatkova, Ondrej Cinek, Lenka Dusatkova, Tomas Dedic, Tomas Seeman, Jan Lebl, Stepanka Pruhova
Radana Kotalova, Petra Dusatkova, Ondrej Cinek, Lenka Dusatkova, Tomas Dedic, Tomas Seeman, Jan Lebl, Stepanka Pruhova, Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, 15006 Prague, Czech Republic
Author contributions: Kotalova R and Dedic T provided the clinical care; Dusatkova P, Cinek O, Dusatkova L, Seeman T and Pruhova S performed the research and contributed to the manuscript preparation; Kotalova R, Dedic T and Lebl J wrote the paper; all co-authors review the paper prior to submission.
Supported by Grants No. NT11457 and No. NT11402 (to IGA MZ CR); and grant from Research project (Ministry of Health Care, Czech Republic) of the conceptual development of research organization, No. 00064203 (to FN Motol).
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jan Lebl, Professor, MD, PhD, Chief, Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, V Uvalu 84, 15006 Prague, Czech Republic. jan.lebl@lfmotol.cuni.cz
Telephone: +420-224-432001 Fax: +420-224-432020
Received: July 7, 2014
Peer-review started: July 8, 2014
First decision: August 6, 2014
Revised: August 28, 2014
Accepted: December 1, 2014
Article in press: December 1, 2014
Published online: February 28, 2015
Processing time: 235 Days and 20 Hours
Abstract

Hepatocyte nuclear factor 1-β (HNF1B) defects cause renal cysts and diabetes syndrome (RCAD), or HNF1B-maturity-onset diabetes of the young. However, the hepatic phenotype of HNF1B variants is not well studied. We present a female neonate born small for her gestational age [birth weight 2360 g; -2.02 standard deviations (SD) and birth length 45 cm; -2.40 SD at the 38th gestational week]. She developed neonatal cholestasis due to biliary atresia and required surgical intervention (portoenterostomy) when 32-d old. Following the operation, icterus resolved, but laboratory signs of liver dysfunction persisted. She had hyperechogenic kidneys prenatally with bilateral renal cysts and pancreatic hypoplasia postnatally that led to the diagnosis of an HNF1B deletion. This represents the most severe hepatic phenotype of an HNF1B variant recognized thus far. A review of 12 published cases with hepatic phenotypes of HNF1B defects allowed us to distinguish three severity levels, ranging from neonatal cholestasis through adult-onset cholestasis to non-cholestatic liver impairment, all of these are associated with congenital renal cysts and mostly with diabetes later in life. We conclude that to detect HNF1B variants, neonates with cholestasis should be checked for the presence of renal cysts, with special focus on those who are born small for their gestational age. Additionally, patients with diabetes and renal cysts at any age who develop cholestasis and/or exocrine pancreatic insufficiency should be tested for HNF1B variants as the true etiological factor of all disease components. Further observations are needed to confirm the potential reversibility of cholestasis in infancy in HNF1B mutation/deletion carriers.

Keywords: Hepatocyte nuclear factor 1-β; Renal cysts and diabetes syndrome; Maturity-onset diabetes of the young; Biliary atresia; Portoenterostomy

Core tip: Hepatocyte nuclear factor 1-β (HNF1B) defects cause renal cysts and diabetes syndrome (renal cysts and diabetes; HNF1B-maturity-onset diabetes of the young), but little is known on liver in these patients. We succeeded to detect the most severe hepatic phenotype of an HNF1B gene deletion in a female neonate with cholestasis due to biliary atresia. She required portoenterostomy when 32-d old. She had bilateral renal cysts and pancreatic hypoplasia. A review of 12 published cases allows distinguishing three severity levels of liver impairment in HNF1B defects, ranging from neonatal cholestasis through adult-onset cholestasis to non-cholestatic liver disease. All have renal cysts and later-onset diabetes.