Gene And Clinicalanalysis Of Neonatal Intrahepatic Cholestasis Caused By Citrin Defciency(NICCD)

Objective: To analyse the correlation between SLC25A13 genotype and NICCD biochemical phenotype,so as to provide scientific evidences for deeply-understanding of SLC25A13 function and assessing the prognosis of NICCD.Summarize the differences in clinical characteristics between neonatal intrahepatic cholestasis caused by citrin defciency（NICCD）and idiopathic neonatal cholestasis（INC）,to provide ideas and strategy for early diagnosis and treatment of NICCD.Methods: The clinical manifestation,laboratory data of 30 patients diagnosed of INC and 30 NICCD patients diagnosed by gene detection were collected.The patients all came to Children’s hospital affiliated to chongqing medical university for ‘jaundice’from March 2013 to December2017.Summarize the correlation between NICCD patients SLC25A13 gene mutation types and biochemical characteristics（blood glucose,liver function,bilirubin,blood ammonia,lactic acid,blood amino acid level）.Analyse the differences in clinical manifestation and biochemical data（blood glucose,liver function,bilirubin,bile acid,albumin,blood fat,blood ammonia,lactic acid,alpha-fetoprotein,copper blue protein）、blood amino acid level and urine gas chromatography results between NICCDgroup and INC group.The correlation between NICCD SLC25A13 genotype and biochemical phenotype was assessed by using Fisher’s exact test.The clinical characteristics of NICCD and INC was assessed by T test.P<0.05 as the standard of significance.Results:（1）.7（23.3%）homozygotes mutations,9（30%）compound heterozygotes mutations and 14（46.6%）heterozygotes were detected in 30 NICCD patients.15 types of gene mutations were discovered,while851₈54del（38.3%）,615+5G>A（6.6%）,1638₁660dup23（5%）,IVS16ins3kb（3.3%）were the most common types.（2）.The results of this study indicate,there were no significant correlation between SLC25A13 genotype and NICCD biochemical phenotype（Bilirubin,liver function,blood coagulation,blood glucose,total protein,albumin,copper blue protein,fibrinogen,blood citrulline,methionine,tyrosine,arginine,threonine,and free carnitine）,all P values were over 0.05.（3）.The results of this study indicate,compared with the INC group,NICCD group had signifcantly higher levels of bile acid,blood fat,blood ammonia,AFP,coagulation markers.The blood sugar,transaminase,protein level was signifcantly lower in NICCD group.NICCD group had signifcantly higher levels of blood citrulline,methionine,tyrosine,arginine,threonine and free carnitine than INC group.Urine 4-hydroxyphenylpyruvic acid,4-hydroxybenzoic acid and benzoic acid were signifcantly higher in NICCD group.The above differences were statistically significant.Conclusion:The most common mutation types of SLC25A13 were c.851₈54del,c.615+5G>A,1638₁660dup23,IVS16ins3 kb in Sichuan and Chongqing area.The correlation between NICCD genotype and biochemical type was not found in this study.The results of this study are suggested,we should consider NICCD those who appear delayed healing jaundice,with the bile acid obviously elevated,with Hypoglycemia,lowprotein,hyperlipidemia,high alpha-fetal protein,high blood ammonia,coagulation dysfunction,citrullinemia and urine 4-hydroxyphenylpyruvic acid,4-hydroxybenzoic acid increased.SLC25A13 Genetic testing should be improved early to make a definite diagnosis,and the diet structure should be adjusted as soon as possible to avoid cirrhosis.