Abstract: Objective    To investigate the gene phenotype and early serum bile acid spectrum characteristics of infants with intrahepatic cholestasis caused by Citrin deficiency. Methods    The clinical data of children with cholestasis admitted to the Department of Endocrine Genetic Metabolism in Children，Maternal and Child Health Hospital of Hubei Province from October 2019 to February 2022 were collected.Twenty children with infantile intrahepatic cholestasis caused by Citrin deficiency diagnosed by gene were taken as NICCD group，while 31 children were included as idiopathic neonatal cholestasis（INC） group，and five healthy infants were included as normal control（NC） group. The clinical characteristics and gene results of NICCD group were analyzed retrospectively. At the same time，15 components of bile acids in the three groups were detected by liquid chromatography tandem mass spectrometry（LC-MS/MS），and the bile acid spectrum results of NICCD group，INC group and NC group were compared and statistically analyzed. Results    A total of 8 mutation sites were found in the NICCD group，including 3 new sites：c 1043C>T（p.P348L）、c.1216dupG（p.A406 Gfs*13）and c.135G>C（p.L45F）.The results of bile acid spectrum showed that taurine conjugated chenodeoxycholic acid（TCDCA），glycine conjugated chenodeoxycholic acid（GCDCA）and taurocholic acid（TCA）were significantly increased in the NICCD group，and the differences were statistically significant（F=33.117，15.021，10.175，P<0.05）. Conclusion    The new mutation site expands the SLC25A13 gene spectrum，providing more genetic counseling for the disease.Bile acid spectrum analysis may be a potential method to identify cholestatic liver disease.TCA，TCDCA and GCDCA is helpful to identify NICCD.

Key words: Citrin deficiency, intrahepatic, cholestasis, SLC25A13 gene, bile acid spectrum

摘要： 目的    探讨Citrin蛋白缺陷所致婴儿肝内胆汁淤积症患儿的基因表型及早期血胆汁酸谱特征。方法    收集2019年10月至2022年2月湖北省妇幼保健院儿童内分泌遗传代谢科收治的胆汁淤积症患儿的临床资料，将基因诊断为Citrin蛋白缺陷所致的婴儿肝内胆汁淤积症的患儿20例作为NICCD组，病因未明的31例患儿作为特发性胆汁淤积症（INC）组，选取5名健康婴幼儿作为正常对照（NC）组，回顾性分析NICCD组临床特点及基因结果。同时采用液相色谱串联质谱法（LC-MS/MS）检测3组15种胆汁酸成分，比较NICCD组与INC组及NC组的胆汁酸谱结果并进行统计学分析。结果    NICCD组患儿中共发现8种突变位点，其中新发位点3个，分别为c.1043C>T（p.P348L）、c.1216dupG（p.A406 Gfs*13）、c.135G>C（p.L45F）。胆汁酸谱结果显示牛磺结合型鹅脱氧胆酸（TCDCA）、甘氨结合型鹅脱氧胆酸（GCDCA）、牛磺胆酸（TCA）在NICCD组中明显升高，差异具有统计学意义（F=33.117、15.021、10.175，P<0.05）。结论    新发突变位点扩展了SLC25A13基因谱系，为该病提供更多的遗传咨询。胆汁酸谱分析或可作为鉴别胆汁淤积性肝病的一种潜在检测方法，TCA、TCDCA及GCDCA有助于鉴别NICCD。

关键词: Citrin蛋白缺陷, 肝内, 胆汁淤积, SLC25A13基因, 胆汁酸谱