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

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