Application Analysis Of Tandem Mass Spectrometry Combined With Next Generation Sequencing In Inborn Errors Of Metabolism

Objective: To study and evaluate the application of tandem mass spectrometry and high-throughput sequencing in the diagnosis of inherited metabolic disorders(IEM),so as to provide scientific basis and guidance for medical practice of IEM in this region.Methods: The clinical data,tandem mass spectrometry and high-throughput sequencing results of 120 children with suspected IEM admitted to the Pediatric Center of the First Affiliated Hospital of Xinjiang Medical University from 2018 to 2022 were collected retrospectively.ROC curves were used to evaluate the sensitivity and specificity of tandem mass spectrometry and high-throughput sequencing in the diagnosis of IEM.Results: Of the 120 children with suspected IEM,28(23.3%)were confirmed by clinical manifestations.Among them,15 cases(53.57%)were amino acid metabolic diseases,6cases(21.43%)were organic acidemia,3 cases(10.71%)were fatty acid metabolic diseases,4 cases(14.29%)were other diseases,including hepatolenticular degeneration(1case),fructose-1,6-bisphosphatase deficiency(1 case),dihydropyrimidinase deficiency(1case)and spherocytosis type 2(1 case).Tandem mass spectrometry showed that 41 cases(31.6%)suggested genetic metabolic diseases,with a sensitivity of 96.43%,a specificity of 84.78%,a positive predictive value of 65.85% and a negative predictive value of98.73%.The results of high-throughput sequencing showed that 29 patients(23.3%)were suggested to have inherited metabolic diseases,and the sensitivity,specificity,positive predictive value and negative predictive value of high-throughput sequencing were 100%,98.91%,96.55% and 100%,respectively.Among them,the results of tandem mass spectrometry were inconsistent with those of high-throughput sequencing in 4 children.Conclusion: Tandem mass spectrometry testing can provide rapid initial screening,while high-throughput sequencing can provide in-depth analysis of gene mutations and related gene dysfunction.The combined application can improve the accuracy and comprehensiveness of diagnosis,more accurately diagnose suspected genetic metabolic diseases,explain the etiology from the genetic level,and provide guidance for further treatment and genetic counseling.