Screening Of Sensitive Mutations And Changeable Biochemical Characters Of Neonatal Intrahepatic Cholestasis In Chinses Patients Caused By Citrin Deficiency

Objective:In the present paper, we focused on observing the relationships between sensitive mutations and metabolic changes in Neonatal Intrahepatic Cholestasis Caused By Citrin Deficiency (NICCD), associated with heterozygous, homozgous and hybrid individuals. Our results would provide corresponding parameters for the early diagnosis of NICCD.Methods:High Resolution Melting (HRM) was used to screen patients involving mutation sites of851del4,1638ins23, IVS6+5G>A and IVS16ins3kb from NICCD. A series of measurements were applied to appraise for the populations such as metabolic indices of liver, hepatase, blood ammonia, lactic acid, AFP and blood fat. Moreover, the values of hepatic metabolism were detected, included in ultrasound, metabolic lactose, urine tyrosine. metabolism of amino acid, and carnitine by Gas Chromatograph Mass Spectrometer (GC/MS) and tandem mass spectrometry(MS/MS).Results:27neonates with NICCD, a total of360cases, were testified (the positive rate was7.5%) in the current study. Mutation rates were presented in those27cases as follows:851del4(50.0%),1638ins23(13.0%), IVSI6ins3kb (7.4%) and IVS6+5GA (7.4%). Interestingly, the expression levels of TBIL, DBIL, GPT, GOT and lactic acid were significantly increased in the patients, compared with the scores of blood ammonia (95.2%), AFP (95.2%), bile acid (90.0%), low protein (84.0%), blood fat (50.0%), galactose (78.3%),4-hydroxyl phenyllactic acid (52.2%,), C14(84.7%), C16(71.4%) and citrulline (66.7%).Conclusion:851de14, the most sensitive mutation site, was observed in this experiment. And then, the gradually decreased scores of mutation sites was1638ins23, Ivs16ins3kb and IVS6+5G>A. No significant correlation was observed among the contents of melons, tyrosine, phenylalanine, C2-carnitine, C14, and C16in both homozygous mutants and heterozygous individuals. However, the significantly biochemical changes were detected in three-month old neonates with NICCD. The increasing metabolism disorders were presented in contents of amino acids, fatty acid, half of lactose, melon acid and long chain acy in our experiments.