新生儿肝内胆汁淤积症的质谱分析和SLC25A13基因检测  

Mass spectrometry and SLC25A13 gene analysis of neonatal intrahepatic cholestasis caused by citrin deficiency

作　　者：谢莉 陈大宇[1,2,3] 潘莉珍 谭建强[1,2,3] 黄钧 严提珍 蔡稔[1,2,3] 郑敏 XIE Li;CHEN Dayu;PAN Lizhen;TAN Jianqiang;HUANG Jun;YAN Tizhen;CAI Ren;ZHENG Min(Liuzhou Maternity and Child Healthcare Hospital,Liuzhou,Guangxi 545001,China;Liuzhou Institute of Reproduction and Genetics,Liuzhou,Guangxi 545001,China;Affiliated Maternity Hospital and Affiliated Children’s Hospital of Guangxi University of Science and Technology,Liuzhou,Guangxi 545001,China;Guangzhou Women and Children’s Medical Center,Guangzhou,Guangdong 510000,China)

机构地区：[1]柳州市妇幼保健院,广西柳州545001 [2]柳州市生殖与遗传研究所,广西柳州545001 [3]广西科技大学附属妇产医院、儿童医院,广西柳州545001 [4]广州市妇女儿童医疗中心,广东广州510000

出　　处：《中国优生与遗传杂志》2021年第9期1323-1327,共5页Chinese Journal of Birth Health & Heredity

基　　金：广西壮族自治区卫生和计划生育委员会科研课题(Z2016548);柳州市科技计划项目(2018AF10501)。

摘　　要：目的对新生儿肝内胆汁淤积症(NICCD)患儿进行血液生化、血串联质谱、尿气相色谱质谱技术分析,同时进行SLC25A13基因突变分析,了解有无citrin缺陷,为NICCD的鉴别诊断提供思路。方法对我院就诊的127例特发性胆汁淤积症患儿进行肝功能、总胆汁酸、甲胎蛋白、凝血功能等生化指标检测,结合血串联质谱、尿气相质谱分析,对怀疑为citrin缺陷病的患儿采用Sanger测序技术分析SLC25A13基因突变情况。结果 127例特发性胆汁淤积症患儿经血串联质谱、尿气相质谱分析,其中有7例患儿的血瓜氨酸、尿4-羟基苯乳酸及4-羟基苯丙酮酸均显著增高,同时血清总胆汁酸、甲胎蛋白水平显著升高,血氨浓度不同程度异常,这7例患儿考虑为NICCD,其中4例进行SLC25A13基因检测,4例(占100%)SLC25A13基因突变类型均为c.851-854del GTAT/c.851-854del GTAT纯合突变。7例NICCD中,5例(71.4%)苏氨酸、蛋氨酸增高,4例(57.1%)精氨酸水平增高,4例(57.1%)游离肉碱轻度升高。结论 citrin缺陷是我国NICCD患儿的重要原因,对于病因不明的胆汁淤积症患者,需早期完善血尿串联质谱及相关基因检测明确病因。本地区SLC25A13基因常见的突变类型为c.851-854del GTAT。Objective Blood biochemistry, blood tandem mass spectrometry and urine gas chromatography-mass spectrometry were performed on neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD), and SLC25A13 gene mutation was analyzed to understand whether there was citrin deficiency, so as to provide ideas for the differential diagnosis of NICCD. Methods The liver function, total bile acid, alpha-fetoprotein, coagulation function and other biochemical indexes of 127 children with NICCD admitted to our hospital were tested. The SLC25A13 gene mutation was analyzed by Sanger sequencing technology in the children suspected to be with citrin deficiency. Results 127 cases of children with NICCD were analyzed by blood tandem mass spectrometry, urine gas phase mass spectrometry analysis. 7 cases of blood citrulline significantly increased, urine lactic acid and 4-4-hydroxy benzene hydroxyl benzene pyruvic acid significantly increased, while the marked increase in serum levels of total bile acid, AFP, abnormal blood ammonia concentration in different degree. The 7 cases of NICCD, four of them were performed with SLC25A13 gene tests. It is found that the four(100%) SLC25A13 gene mutation types were c851-854 del GTAT/c.851-854 del GTAT homozygous mutation. Among the 7 cases of NICCD, threonine and methionine of 5 cases(71.4%) increased, arginine level of 4 cases(57.1%) increased, and free carnitine of 4 cases(57.1%)slightly increased. Conclusion citrin deficiency is an important cause of NICCD in China. For patients with infant cholestasis whose etiology is unknown, it is necessary to improve the hematuria tandem mass spectrometry and related gene detection to determine the etiology at an early stage. The common mutation type of SLC25A13 gene in this region is c.851-854 del GTAT.

关 键 词：新生儿胆汁淤积症 串联质谱 尿气相色谱质谱 CITRIN缺陷 

分 类 号：R722.1[医药卫生—儿科]