以肝病为首发表现的肝豆状核变性患儿的临床特征及基因变异分析  

Clinical features and genetic variants of children with hepatic Wilson′s disease

作　　者：王美娟[1] 钟雪梅[1] 马昕[1] 宁慧娟[1] 朱丹[1] 宫幼喆[1] Wang Meijuan;Zhong Xuemei;Ma Xin;Ning Huijuan;Zhu Dan;Gong Youzhe(Department of Gastroenterology,Children′s Hospital,Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院消化内科,北京100020

出　　处：《中华全科医师杂志》2023年第8期839-843,共5页Chinese Journal of General Practitioners

摘　　要：目的:分析北京及周边地区以肝病为首发表现的肝豆状核变性(WD)患儿的临床特征及基因突变情况。方法:本研究为回顾性单中心研究。回顾性收集并分析2018年3月至2022年3月在首都儿科研究所附属儿童医院体检以肝病为首发表现的35例WD患儿的临床资料及基因检测结果,并根据致病基因突变类型分组比较患儿的临床特征。结果:35例WD患儿中,男24例,女11例,中位确诊年龄为5.5(4.0,7.5)岁。所有患儿均有转氨酶增高,其中33例(94.3%)为入托、入学或其他疾病常规体检时发现转氨酶升高,就诊前2周内均无发热、咳嗽,无反复呕吐、腹痛、腹泻,无皮肤黄染,无肢体震颤、步态不稳等不适,仅1例有恶心症状;其余2例中,1例11岁患儿因浮肿就诊,经检查患儿已出现肝硬化门脉高压食管静脉曲张;另1例7岁患儿因恶心、黄疸就诊,以急性肝衰竭起病。33例(94.3%)患儿铜蓝蛋白水平<100 mg/L,16例(45.7%)患儿24 h尿铜>100μg,2例(5.7%)患儿24 h尿铜<40μg。35例患儿乙型肝炎病毒、丙型肝炎病毒、巨细胞病毒、EB病毒等病原学检测均阴性,自身免疫性肝炎抗体均阴性。33例体检发现转氨酶异常的WD患儿中,5例(15.2%)腹部超声检查结果未见异常,余患儿存在不同程度肝大、脾大、肝实质回声增强等表现。35例患儿共检测到34种不同的ATP7B等位基因突变,最常见的基因突变位点依次为8号外显子c.2333G>T(P.R778L)、11号外显子c.2621C>T(p.A874V)及13号外显子c.2975C>T(p.P992L)。含有无义、移码或剪接突变的患儿与仅存在错义突变的患儿相比,年龄、转氨酶及24 h尿铜水平比较差异均无统计学意义(Z=-1.00,t=-0.16,Z=-1.14,Z=-1.03,均P>0.05)。结论:儿童WD起病隐匿,对转氨酶升高的患儿需警惕本病,及时进行铜蓝蛋白及尿铜检测,不同基因型WD患儿临床表型未见差异。Objective To analyze the clinical characteristics and genetic variants of children with hepatic Wilson disease(WD).Methods The clinical data and genetic test results of 35 children,who were diagnosed as WD with primary hepatic manifestation in the Department of Gastroenterology,Children′s Hospital of Capital Institute of Pediatrics from March 2018 to March 2022,were retrospectively analyzed.The relationship between phenotype and genotype of patients was analyzed.Results Among 35 children,there were 24 males and 11 females with a median age at diagnosis of 5.5(4.0,7.5)years.All patients had elevated transaminases.The elevated transaminases was found during routine physical examination in 33 cases(94.3%),in whom there was no fever,cough,recurrent vomiting,abdominal pain,diarrhea,jaundice,limb tremor,gait instability and other discomfort 2 weeks before admission,except 1 case with nausea;abdominal ultrasonography showed that 5 cases(15.2%)had no abnormality,and others had different degrees of hepatomegaly,splenomegaly,and echo enhancement in liver parenchyma.Among the remaining 2 cases,one 11-year-old child presented with edema,and had cirrhosis portal hypertension with esophageal varices;another 7-year-old child was diagnosed as acute liver failure manifested with nausea and jaundice.Thirty three patients(94.3%)had decreased serum ceruloplasmin levels(<100 mg/L);24-h urinary copper concentration was>100μg in 16 cases(45.7%)and<40μg in 2 cases(5.7%).The tests of hepatitis B virus,hepatitis C virus,cytomegalovirus and EB virus were all negative in 35 children,and the autoimmune hepatitis antibodies were also negative.A total of 34 different ATP7B gene mutations were detected;the most frequent mutation was c.2333G>T(P.R778L)at exon 8,followed by c.2621C>T(p.A874V)at exon 11 and c.2621C>T(p.A874V)at exon 13.There was no significant difference in clinical phenotype between patients with nonsense mutation,frameshift mutation or splicing mutation and those with only missense mutations(Z=-1.00,t=-0.16,Z=-1.14,Z=-1.03,a

关 键 词：肝豆状核变性 临床表现 基因型 儿童 

分 类 号：R725.7[医药卫生—儿科]