湖北地区 Citrin 缺陷导致的新生儿肝内胆汁淤积症临床研究  

Clinical research of neonatal intrahepatic cholestasis caused by Citrin deficiency in Hubei Province

作　　者：熊小丽[1] 鄢素琪[1] 丁艳[1] 周俪姗[1] 陈鹏[1] 赵东赤[2] 

机构地区：[1]武汉市儿童医院儿内科,430016 [2]武汉大学中南医院儿科,430016

出　　处：《中华实用儿科临床杂志》2015年第14期1064-1068,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金（81403434）;武汉市青年科技晨光计划项目（201150431082）

摘　　要：目的：探讨湖北地区 Citrin 缺陷导致的新生儿肝内胆汁淤积症（NICCD）的临床表现及实验室特点。方法收集2010年9月至2013年1月在武汉市儿童医院住院20例 NICCD 患儿未经治疗时的生化指标（肝功能、血脂、乳酸、血氨、总胆汁酸、甲胎蛋白）、凝血象、血氨基酸谱、酰基肉碱谱、尿有机酸谱及 SLC25A13基因分析，并随访1年。结果 NICCD 患儿实验室检查表现为高胆红素血症、肝酶升高、胆汁酸增高，高脂血症、高甲胎蛋白、高乳酸血症、高氨血症、低蛋白血症、低血糖、凝血机制障碍；多种氨基酸升高，以瓜氨酸升高为主；酰基肉碱中以长链酰基肉碱升高为主；尿4-羟基苯乙酸、4-羟基苯乳酸、4-羟基苯丙酮酸异常增高；SLC25A13基因分析共发现6个突变位点，其中 L477R，G639S 为新发突变位点，851del4、1638ins23、IVS6＋5G ﹥A 为热点突变。20例患儿黄疸均在1岁内缓解。结论 NICCD 患儿多项临床实验指标异常，高脂血症在病程早期即已出现，L477R、G639S 为新发突变位点。Objective To explore the clinical manifestations and the characteristics of neonatal intrahepatic cholestasis caused by Citrin deficiency（NICCD）in Hubei province. Methods The biochemical indicators including liver function,blood lipid,lactic acid,blood ammonia,total bile acid,alpha feto protein,coagulogram,blood amino spec-trum,acylcrnitine spectrum,urine organic acid and SLC25A13 gene analysis of 20 cases with NICCD,who came from Wuhan Children＇s Hospital,during September 2010 to January 2013,were collected before treatment,then followed up for 1 year. Results Laboratory results of NICCD patients showed high blood bilirubin,elevated liver enzymes and bile acid,hyperlipidemia,high alpha feto protein,high lactic acidosis,high ammonia,hypoalbuminemia,hypoglycemia,disor-der of blood coagulation mechanism,variety of amino acids increase,mainly citrulline rose. Mainly long - chain acyl carnitine increased among acyl of carnitine. Abnormal increase of urine 4 - hydroxy benzene acetic acid,4 - hydroxy benzene lactic acid and 4 - hydroxy benzene pyruvic acid. Six mutations were detected in SLC25A13 gene analysis,and L477R,G639S of them were novel mutations,851del4,1638ins23,IVS6 ＋ 5G ﹥ A were hot mutation. All the patients were eased in jaundice before they were 1 year old. Conclusions The early clinical criterion of the patients is disor-der. Hyperlipidemia has been detected in the early course of the disease,and L477R,G639S are the novel mutations.

关 键 词：CITRIN 缺陷 新生儿肝内胆汁淤积症 SLC25A13 

分 类 号：R722.1[医药卫生—儿科]