Acute liver failure with hemolytic anemia in children with Wilson’s disease:Genotype-phenotype correlations?

作     者：Tudor Lucian Pop Alina Grama Ana Cristina Stefanescu Claudia Willheim Peter Ferenci 

作者机构：2^(nd) Pediatric DisciplineDepartment of Mother and ChildIuliu Hatieganu University of Medicine and PharmacyCluj-Napoca 400177Romania 2^(nd) Pediatric ClinicCenter of Expertise in Pediatric Liver Rare DisordersEmergency Clinical Hospital for ChildrenCluj-Napoca 400177Romania Department of Internal Medicine ⅢGastroenterology and HepatologyMedical University of ViennaWien A-1090Austria 

出 版 物：《World Journal of Hepatology》 (世界肝病学杂志（英文版）（电子版）)

年 卷 期：2021年第13卷第10期

页      面：1428-1438页

学科分类：1002[医学-临床医学] 100202[医学-儿科学] 10[医学] 

主　　题：Wilson’s disease Children Acute liver failure Hemolytic anemia ATP7B variant Genotype-phenotype correlation 

摘      要：BACKGROUND Wilson’s disease(WD)is a rare autosomal recessive inherited disorder of copper *** liver failure(ALF)and hemolytic anemia represent the most severe presentation of WD in *** clear genotype-phenotype correlations exist in ***-truncating nonsense,frame-shift,or splice-site variants may be associated with more severe *** contrast,missense variants may be associated with late-onset,less severe disease,and more neurological ***,a gene variant(HSD17B13:TA,rs72613567)with a possible hepatic protective role against toxins was associated with a less severe hepatic phenotype in *** To analyze the possible genotype-phenotype correlations in children with WD presented with ALF and non-immune hemolytic *** The medical records of children with WD diagnosed and treated in our hospital from January 2006 to December 2020 were retrospectively *** clinical manifestations(ALF with non-immune hemolytic anemia or other less severe forms),laboratory parameters,copper metabolism,ATP7B variants,and the HSD17B13:TA(rs72613567)variant were reviewed to analyze the possible genotype-phenotype *** We analyzed the data of 51 patients with WD,26 females(50.98%),with the mean age at the diagnosis of 12.36±3.74 *** and Coombs-negative hemolytic anemia was present in 8 children(15.67%),all adolescent *** Kayser-Fleisher ring was present in 9 children(17.65%).The most frequent variants of the ATP7B gene were ***1069Gln(c.3207AG)in 38.24% of all alleles,***1341Asp(c.4021GA)in 26.47%,***939Cys(c.2817GT)in 9.80%,and ***844Ter(c.2530AT)in 4.90%.In ALF with hemolytic anemia,***939Cys(c.2817GT)and ***844Ter(c.2530AT)variants were more frequent than in other less severe forms,in which ***1069Gln(c.3207AG)was more ***1341Asp(c.4021GA)has a similar frequency in all hepatic *** 33 of the patients,the HSD17B13 genotype was *** overall HSD17B13:TA a