Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2021; 13(10): 1428-1438
Published online Oct 27, 2021. doi: 10.4254/wjh.v13.i10.1428
Acute liver failure with hemolytic anemia in children with Wilson’s disease: Genotype-phenotype correlations?
Tudor Lucian Pop, Alina Grama, Ana Cristina Stefanescu, Claudia Willheim, Peter Ferenci
Tudor Lucian Pop, Alina Grama, Ana Cristina Stefanescu, 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400177, Romania
Tudor Lucian Pop, Alina Grama, 2nd Pediatric Clinic, Center of Expertise in Pediatric Liver Rare Disorders, Emergency Clinical Hospital for Children, Cluj-Napoca 400177, Romania
Claudia Willheim, Peter Ferenci, Department of Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Wien A-1090, Austria
Author contributions: Pop TL performed the study design, literature research, data acquisition and analysis, resources, writing the original draft, reviewed and edited the draft; Grama A and Stefanescu A performed the data acquisition and analysis, reviewed the draft; Willheim C performed the genetic investigations, data acquisition and interpretation, reviewed the draft; Ferenci P performed the study design, data analysis, resources, review of the draft, supervision; all authors have read and approved the final manuscript.
Institutional review board statement: The data analyzed in this manuscript came from research approved by the Emergency Clinical Hospital for Children Cluj-Napoca Institutional Review Board.
Informed consent statement: All involved subjects (or parents or legal representatives) signed a written informed consent that clinical and laboratory data might be used in further research. All details that might disclose the identity of the subjects under study were omitted or anonymized.
Conflict-of-interest statement: Pop TL, Grama A, Stefanescu AC, Willheim C have no conflicting interests related to the present work. Ferenci P reports personal fees from Alexion, personal fees from Univar, personal fees from Vivet Therapeutics, grants from Gilead, during the conduct of the study.
Data sharing statement: No additional data are available.
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: Tudor Lucian Pop, MD, PhD, Associate Professor, 2nd Pediatric Discipline, Department of Mother and Child, Iuliu Hatieganu University of Medicine and Pharmacy, Str. Crisan nr 5, Cluj-Napoca 400177, Romania. tudor.pop@umfcluj.ro
Received: April 30, 2021
Peer-review started: April 30, 2021
First decision: June 17, 2021
Revised: June 23, 2021
Accepted: September 3, 2021
Article in press: September 3, 2021
Published online: October 27, 2021
Processing time: 175 Days and 1.7 Hours
ARTICLE HIGHLIGHTS
Research background

There is a continuous interest in genotype-phenotype correlations in Wilson’s disease (WD).

Research motivation

The aim is to study the possible genotype-phenotype correlations in children with acute liver failure (ALF) and hemolytic anemia in WD.

Research objectives

The objectives include the analysis of ATP7B variants in children with ALF and hemolytic anemia in WD compared to the other clinical presentations and the possible role of the HSD17B13:TA variant in the modulation of the WD severity.

Research methods

The retrospective study included 63 children with WD diagnosed and follow-up during 2006-2020. The clinical manifestations (acute or chronic liver disease, neurologic disease, ALF with non-immune hemolytic anemia), laboratory parameters, copper metabolism, ATP7B variants, and the HSD17B13:TA (rs72613567) variant were reviewed.

Research results

In our cohort, in children with ALF and non-immune hemolytic anemia, the nonsense variants other than p.His1069Gln (c.3206A>G), as p.Trp939Cys (c.2817G>T), and frame-shift variants, as p.Lys844Ter (c.2530A>T), were the most frequently present. The allele frequency of HSD17B13:TA was similar to other results for the Caucasian population, higher in patients with the less severe liver disease than those presented with ALF and hemolytic anemia.

Research conclusions

It remains challenging to prove a genotype-phenotype correlation in WD patients due to the small number of patients in the reported series and the increased genetic heterogeneity. When nonsense, frame-shift, or splicing-site variants are identified in a pre-symptomatic period, the importance of this genotype-phenotype correlation for the prognostic is evident.

Research perspectives

A more extensive study involving children and adolescents with ALF and hemolytic anemia form of WD should be provided to confirm the findings. New studies are needed to evaluate the role of protective variant, HSD17B13:TA (rs72613567), in association with other factors, in less severe forms of WD in children.