Alagille综合征疑诊为先天性胆道闭锁一例并文献复习  

Alagille syndrome misdiagnosed as congenital biliary atresia:a case report and literature review

作　　者：许丁伟 马江云 李新成[1] 黄洁[1] Xu Dingwei;Ma Jiangyun;Li Xincheng;Huang Jie(Department of Hepatobiliary and Pancreatic Surgery,Second Affiliated Hospital of Kunming Medical University,Kunming 650101,China)

机构地区：[1]昆明医科大学第二附属医院肝胆胰外科,650101

出　　处：《中华肝脏外科手术学电子杂志》2023年第6期681-687,共7页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：云南省科技厅昆医联合专项(202001AY070001-229);昆明医科大学第二附属医院院内研究项目(2020yk007)。

摘　　要：目的探讨Alagille综合征的临床特征、诊疗方法及预后情况。方法回顾性分析2022年2月在昆明医科大学第二附属医院行手术治疗的1例疑诊先天性胆道闭锁后确诊Alagille综合征患儿临床资料。患儿男,10岁9个月,"因反复皮肤黄染伴瘙痒10年余,再发加重1周"于2021年11月以"先天性胆道闭锁"收入院。体检:发育明显障碍,头围偏小、前额突出,眼距中度增宽,尖下巴,四肢关节畸形。肝脏肋下3 cm触及,质软。ALT、AST、TB、DB、ALP、GGT等肝功能指标不同程度升高。MRCP示肝内胆管分支不清,未见扩张,肝外胆管纤细,特异性胆管炎可能。超声检查示胆管纤细,肝损伤声像。ERCP示胆总管线性狭窄、肝总管囊状扩张。检索万方、维普、CNKI、PubMed、MEDLINE数据库中儿童Alagille综合征相关文献,并进行总结分析。结果2021年11月25日患者行胆管支架胆道植入术,术后3 d腹痛剧烈,急诊行胆管支架取出,同时行PTCD。多学科讨论后行血液全外显子靶向捕获-高通道测序,结果显示JAG1基因的c.439C>T(p.Q147^(*))变异,JAG1基因的编码区域检测到1个杂合无义变异。该变异导致JAG1基因第147位密码子由编码谷氨酰胺变为终止密码子。根据患者存在JAG1基因突变,且有前额突出、眼距增宽的特殊面容和慢性胆汁淤积两种典型表现,明确诊断为ALGS。结论ALGS在临床中非常罕见,往往导致漏诊、误诊,且预后较差。基因检测普及使更多ALGS患者得到准确诊断,大部分患者由于心脏疾病或重症肝炎死亡,尚无良好的治疗方案,主要为对症支持治疗,肝移植可能是目前最好的治疗方案。Objective To investigate clinical characteristics,diagnosis,treatment and prognosis of Alagille syndrome(ALGS).Methods Clinical data of 1 child with ALGS misdiagnosed as congenital biliary atresia undergoing surgery in the Second Affiliated Hospital of Kunming Medical University in February 2022 were retrospectively analyzed.The boy,aged 10 years and 9 months,was admitted and diagnosed with"congenital biliary atresia"in our hospital in November 2021 due to"repeated yellow skin complicated with itching for more than 10 years and then aggravated for 1 week".Physical examination showed significant developmental disorder,small head circumference,prominent forehead,moderate hypertelorism,pointed chin and limb joint deformity.The liver was tender and palpable 3 cm below the right costal margin.ALT,AST,TB,DB,ALP,GGT levels and other liver function indexes were increased to varying degrees.MRCP showed that intrahepatic bile duct branches were unclear,no dilatation was found and extrahepatic bile ducts were thin.The possibility of specific cholangitis was considered.Ultrasound examination indicated the signs of thin bile ducts and liver injury.ERCP showed linear stenosis of common bile duct and cystic dilatation of common hepatic duct.Relevant studies of pediatric ALGS were searched from Wanfang Data,Chongqing VIP,CNKI,PubMed and MEDLINE and subject to literature review.Results On November 25,2021,the patient underwent biliary stent implantation,and developed severe abdominal pain at postoperative 3 d.The biliary stent was emergently removed and PTCD was performed simultaneously.After multi-disciplinary team consultation,the whole-exome capture for targeted high-throughput sequencing detected c.439C>T(p.Q147^(*))mutation of JAG1 gene,and heterozygous nonsense mutation in the coding region of JAG1 gene,leading to the change of codon 147 of JAG1 gene from coding glutamine to stop codon.According to JAG1 gene mutation in combination with protruded forehead,two typical manifestations of hypertelorism and chronic cholestasis,t

关 键 词：ALAGILLE综合征 先天性胆道闭锁 诊断 治疗 JAG1基因 

分 类 号：R575[医药卫生—消化系统]