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Targeted Metabolomics Reveals Birth Screening Biomarkers for Biliary Atresia in Dried Blood Spots.

Early diagnosis and timely surgical Kasai portoenterostomy greatly improve the survival of patients with biliary atresia (BA), a neonatal cholestatic disease, which has encouraged investigators to develop newborn screening for BA. In this study, we used ultraperformance liquid chromatography-triple quadrupole mass spectrometry-based targeted metabolomics profiling to identify potential BA biomarkers in dried blood spots (DBS) collected from BA patients (n = 21) and healthy controls (n = 100). A distinctive metabolic profile comprising eight significantly differentially expressed metabolites, taurohyocholic acid (THCA), glutamic acid, 2-hydroxyglutaric acid, ketoleucine, indoleacetic acid, alpha-ketoisovaleric acid, glycocholic acid, and taurocholic acid (TCA), clearly distinguished BA infants from control neonates. Three metabolites, THCA, 2-hydroxyglutaric acid, and indoleacetic acid, were selected using linear regression and receiver operating characteristic (ROC) curve analysis and model construction. The area under the ROC curve for this model to discriminate between BA and comparison infants was 0.938 (95% confidence interval, CI: 0.874-1.000). A cutoff value of -0.336 produced a sensitivity of 90.48% (95% CI: 69.62% - 98.83%) and specificity of 92% (95% CI: 84.84% - 96.48%). In conclusion, the results suggest that metabolic markers in DBS obtained from newborns have a great potential for BA screening.