血浆氨基酸谱变化在Citrin缺陷致新生儿肝内胆汁淤积症诊断中的价值

Value of the changes of plasma amino acids in diagnosis of neonatal intrahepatic cholestasis caused by Citrin deficiency

目的探讨血浆氨基酸谱变化在诊断Citrin缺陷致新生儿肝内胆汁淤积症(NICCD)中的价值。方法收集2016年1月至2018年12月江西省儿童医院住院诊断为婴儿胆汁淤积症,并行血串联质谱检测的患儿,共入组144例。其中NICCD组(11例),胆道闭锁组40例(BA组),巨细胞病毒性肝炎(淤胆型)93例(CMV组)。比较3组患儿血浆氨基酸及生化结果,并采用Kruskal-Wallis检验对3组所检测项目进行数据统计分析,并将经上述统计分析具有统计学差异的项目再行2组间Mann-Whitney检验。结果与BA组及CMV组比较,NICCD组精氨酸(Arg)、甲硫氨酸(Met)、酪氨酸(Tyr)、瓜氨酸(Cit)、转氨酶比(AST/ALT)水平明显升高,同时丙氨酸(Ala)水平下降,差异均有统计学意义(均P<0.05)。NICCD组Arg、Met、Tyr、Cit、AST/ALT、Ala水平分别为68.518(19.714,108.470)μmol/L、111.724(42.156,214.585)μmol/L、104.394(75.642,146.086)μmol/L、165.664(119.874,291.327)μmol/L、3.17(1.97,3.98)、140.297(112.052,184.015)μmol/L;BA组Arg、Met、Tyr、Cit、AST/ALT、Ala水平分别为29.470(10.739,48.124)μmol/L、32.938(24.918,44.013)μmol/L、78.244(66.814,94.479)μmol/L、23.698(19.450,27.714)μmol/L、1.54(1.23,1.95)、244.246(214.554,295.729)μmol/L,CMV组Arg、Met、Tyr、Cit、AST/ALT、Ala水平分别为16.507(8.220,28.566)μmol/L、30.997(23.739,37.183)μmol/L、76.120(64.004,86.290)μmol/L、21.272(17.040,24.111)μmol/L、1.19(0.96,1.48)、228.468(191.131,260.056)μmol/L。受试者工作特征曲线(ROC曲线)显示,Ala、Arg、Met、Tyr、Cit、AST/ALT诊断NICCD曲线下面积分别为0.886、0.770、0.906、0.745、0.999、0.887。结论血浆氨基酸谱变化为NICCD早期诊断提供依据,其中以Arg、Met、Tyr、Cit升高及Ala降低诊断价值高,结合生化改变程度有助临床诊断该病,减少误诊。

Objective To explore the value of changes of plasma amino acids in the diagnosis of neonatal intrahepatic cholestasis caused by Citrin deficiency(NICCD).Methods A total of 144 infants diagnosed with cholestasis and undergoing blood tandem mass spectrometry in Jiangxi Children′s Hospital From January 2016 to December 2018 were studied.They were divided into 3 groups:NICCD group(11 cases),biliary atresia group(BA group,40 cases),and Cholestatic Cytomegalovirus hepatitis group(CMV group,93 cases).The plasma amino acids and biochemical results of the 3 groups were compared,and the data of the 3 groups were statistically analyzed by Kruskal-Wallis test.The items with statistical discrepancy were examined by Mann-Whitney test between groups.Results Compared with BA group and CMV group,the levels of arginine(Arg),methionine(Met),tyrosine(Tyr),citrulline(Cit),glutamic oxaloacetic transaminase and glutamic-pyruvic transaminase ratio(AST/ALT)in NICCD group increased significantly,while the level of alanine(Ala)decreased.The above discrepancy were statistically significant(all P<0.05).The Arg,Met,Tyr,Cit,AST/ALT,and Ala levels of NICCD group were 68.518(19.714,108.470)μmol/L,111.724(42.156,214.585)μmol/L,104.394(75.642,146.086)μmol/L,165.664(119.874,291.327)μmol/L,3.17(1.97,3.98),and 140.297(112.052,184.015)μmol/L,respectively.The Arg,Met,Tyr,Cit,AST/ALT,and Ala levels of BA group were 29.470(10.739,48.124)μmol/L,32.938(24.918,44.013)μmol/L,78.244(66.814,94.479)μmol/L,23.698(19.450,27.714)μmol/L,1.54(1.23,1.95),and 244.246(214.554,295.729)μmol/L,respectively.The Arg,Met,Tyr,Cit,AST/ALT,and Ala levels of CMV group were 16.507(8.220,28.566)μmol/L,30.997(23.739,37.183)μmol/L,76.120(64.004,86.290)μmol/L,21.272(17.040,24.111)μmol/L,1.19(0.96,1.48),and 228.468(191.131,260.056)μmol/L,respectively.In the receiver operating characteristic(ROC)curve,the area under the ROC curve of Ala,Arg,Met,Tyr,Cit and AST/ALT in diagnosing NICCD were 0.886,0.770,0.906,0.745,0.999,and 0.887,respectively.Conclusions The changes of plasma amino acids provides a basis for early diagnosis of NICCD.Elevated Arg,Met,Tyr,Cit and decreased Ala have high diagnostic value of NICCD.Combined with the degree of biochemical changes,plasma amino acids can help with clinical diagnosis of the disease and reduce the misdiagnosis rate.