基于串联质谱和气相色谱-质谱技术分析甲基丙二酸血症患儿代谢谱特征及联合诊断效能OA

Objective To investigate the diagnostic value of tandem mass spectrometry(MS/MS)combined with gas chromatography-mass spectrometry(GC/MS)for methylmalonic acidemia(MMA).Methods A total of 47 children with MMA admitted to the Third Affiliated Hospital of Zhengzhou University from December 2021 to December 2025 were selected as MMA group,and 47 healthychildren undergoing physical examinations during the same period were selected as control group.MS/MS and GC/MS were used to detect blood amino acid and acylcarnitine metabolic profiles and urinary organic acid metabolic profiles,respectively.The general data and differences in blood and urinary metabolic profiles were compared between the two groups.Spearman rank correlation analysis was used to analyze the correlations between blood and urinary metabolic indicators.Variance inflation factor was used to evaluate multicollinearity among independent variables,and a combined diagnos-tic model was constructed using binary Logistic regression.Receiver operating characteristic(ROC)curves were plotted to analyze the diagnostic efficacy of single indicators and combined approaches,and model stability was evaluated.Results The blood amino acid and acylcarnitine metabolites C3,C3/C0,C3/C2,and C3/MET in the MMA group were all higher than those in the control group,with median differences of 6.73 μmol/L,0.39,0.49,and 0.37,respectively,and the differences were statistically significant(P＜0.001).The urinary organic acid metabolites methyl-malonic acid,methylcitric acid,and 3-hydroxypropionic acid in the MMA group were all higher than those in the control group,with median differences of 51.52,2.09,and 1.20 μg/μmol,respec-tively,and the differences were statistically significant(P＜0.001).Spearman correlation analysis showed that blood C3,C3/C0,C3/C2,and C3/MET were all positively correlated with urinary methylmalonic acid,methylcitric acid,and 3-hydroxypropionic acid(P＜0.001).Among them,blood C3/C2 showed the strongest correlation with urinary methylmalonic acid(r=0.818,P＜0.001).The ROC curve results for single indicators showed that the AUCs of C3,C3/CO,C3/C2,and C3/MET were 0.925(95％CI:0.875-0.975),0.937(95％CI:0.889-0.984),0.951(95％CI:0.907-0.995),and 0.949(95％CI:0.910-0.989),respectively,with sensitivities of 97.9％,87.2％,89.4％,and 95.7％,and specificities of 78.7％,89.4％,93.6％,and 83.0％,respectively.The AUC of the combined model of the fourblood indicators was 0.966(95％CI:0.937-0.995),with a sensitivity of 87.2％and a specificity of 93.6％.The AUC of the integrat-ed blood-urine model was 0.990(95％CI:0.976-1.000),with both sensitivity and specificity of 97.9％.DeLong's test showed that the AUC of the integrated blood-urine model was significantly higher than that of the combined model of the four blood indicators(Z=2.202,P=0.028).The results of five-fold cross-validation showed that the AUCs of the integrated blood-urine model in the five validations were 1.000,1.000,0.989,0.944,and 1.000,respectively,with an average AUC of 0.987(95％CI:0.944-1.000),a sensitivity of 94.7％,a specificity of 98.9％,and an accu-racy of 96.8％,indicating that the model had good stability.Conclusion The levels of blood C3,C3/C0,C3/C2,C3/MET and urinary methylmalonic acid,methylcitric acid,and 3-hydroxypropionic acid are significantly elevated in children with MMA.The combined detection of MS/MS and GC/MS has higher diagnostic efficacy for MMA.It is recommended that blood and urinary mass spectrometry be synchronously tested when recalling children with positive initial screening results in areas with a high incidence of MMA,so as to shorten the cycle of differential diagnosis and treatment.