Citrin缺陷致新生儿肝内胆汁淤积症临床特征与SLC25A13基因突变分析  

Analysis of clinical characteristics and SLC25A13 gene mutation in children with neonatal intrahepatic cholestasis caused by citrin deficiency

作　　者：卫慧静 李亚绒[1] 彭晓康[1] 车凤玉 雷玲侠[1] 李瑞娜[1] 刘小乖[1] Wei Huijing;Li Yarong;Peng Xiaokang;Che Fengyu;Lei Lingxia;Li Ruina;Liu Xiaoguai(The Third Department of Children′s Infectious Diseases,Xi′an Children′s Hospital,Xi′an 710003,China;The Institute of Pediatric Diseases of Shaanxi Province,Xi′an 710003,China)

机构地区：[1]西安市儿童医院感染三科,710003 [2]陕西省儿科疾病研究所,西安710003

出　　处：《国际儿科学杂志》2021年第5期353-357,共5页International Journal of Pediatrics

基　　金：西安市卫生健康委员会项目(J201902036)。

摘　　要：目的分析Citrin缺陷致新生儿肝内胆汁淤积症(neonatal intrahepatic cholestasis caused by citrin deficiency,NICCD)的临床特征及SLC25A13基因突变情况。方法收集2014年1月至2018年12月西安市儿童医院确诊NICCD的病例资料,分析其临床表现、生化指标、SLC25A13基因突变和预后。结果18例患儿均来自北方地区,初诊日龄为(63.4±19.5)d,临床表现包括黄疸(100%)、浅色大便(38.9%)、生长落后(27.8%)等。所有患儿均存在胆汁淤积,谷氨酰转肽酶、总胆汁酸和甲胎蛋白均升高,血清白蛋白均降低,伴天冬氨酸氨基转移酶升高(94.4%)、丙氨酸氨基转移酶升高(72.2%)、凝血酶原时间延长(88.9%)、高乳酸血症(83.3%)、低血糖(77.8%)、贫血(66.7%)等多种生化异常。血串联质谱均以瓜氨酸等多种氨基酸升高为特点,70%(7例/10例)尿气相色谱存在4-羟基苯乳酸和4-羟基苯丙酮酸升高。年龄与总胆汁酸呈负相关(r=-0.469,P=0.049),与血氨、苏氨酸、甲硫氨酸、鸟氨酸、酪氨酸呈正相关(r分别为0.472、0.690、0.698、0.678、0.769,P均<0.05)。共检出16种SLC25A13基因突变,c.851_854del(33.3%)和c.1638_1660dup(19.4%)最常见,c.1841+3_1841+4del、c.980_981del(p.E327Vfs*45)和c.602A>T(p.E201V)是未报道的新突变。随访的17例患儿中1例死亡、16例生化指标在1岁内正常。结论特征性生化改变有助于NICCD的早期识别。该病尽早治疗预后多良好。c.851_854del和c.1638_1660dup是北方地区SLC25A13基因的高频突变。Objective To analyze the clinical characteristics and SLC25A13 gene mutation in children with neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD).Methods The data of 18 children diagnosed with NICCD in Xi′an Children′s Hospital from January 2014 to December 2018 were collected.The clinical manifestations,biochemical characteristics,SLC25A13 gene mutation and prognosis were analyzed.Results All the 18 cases of NICCD were from North China and the age of initial diagnosis averaged(63.4±19.5)days.The clinical manifestations included jaundice(100%),light yellow or white stool(38.9%),growth retardation(27.8%)and so on.All patients had cholestasis.Of 18 cases,the levels of glutamyltranspeptidase,total bile acid and alpha fetoprotein were all increased,and serum albumin was decreased.Elevated aspartate aminotransferase(94.4%),elevated glutamic pyruvic transaminase(72.2%),prolonged prothrombin time(88.9%),hyperlactemia(83.3%),hypoglycemia(77.8%),anemia(66.7%)and other biochemical abnormalities were observed.Citrulline and other serum amino acids of all cases were elevated in blood samples by tandem mass spectrometry.The increase of 4-hydroxyphenyllactate and 4-hydroxyphenylpyruvate was found in 70%(7/10)urine samples by gas chromatography.Age was negatively correlated with total bile acid(r=-0.469,P=0.049),and positively correlated with blood ammonia,threonine,methionine,ornithine and tyrosine(r=0.472,0.690,0.698,0.678 and 0.769,respectively,P<0.05).A total of 16 SLC25A13 gene mutations were detected,of them c.851_854del(33.3%)and c.1638_1660dup(19.4%)were the most common.c.1841+3_1841+4del,c.980_981del(p.E327Vfs*45)and c.602A>T(p.E201V)were novel mutations.Among the 17 children who were followed up,1 case died and 16 cases had normal biochemical parameters within 1 year.Conclusion The characteristic biochemical changes are helpful for early recognition of NICCD.The prognosis of NICCD is good if the treatment is appropriate and timely.c.851_854del and c.1638_1660dup are high-frequency mutations of SL

关 键 词：Citrin缺陷症 新生儿肝内胆汁淤积症 SLC25A13基因突变 串联质谱 气相色谱 

分 类 号：R722.1[医药卫生—儿科]