ABSTRACT:
The objective of this study was to indicate the potential of the stable labeled internal standards liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, as a diagnostic method for the detection and confirmation of inherited metabolic diseases (IMDs) in sick infants. A total of 2050 dried blood spot samples of sick infants with suspected IMDs were routinely analyzed by tandem mass spectrometry (MS/MS). Samples showing positive results of particular IMDs were further measured by LC-MS/MS using labeled internal standards to confirm the diagnosis and to determine accurately the concentrations of the diagnostic biomarkers in the provided samples. Labeled internal standards LC-MS/MS method has confirmed the diagnosis of IMDs in 19 symptomatic infants with metabolic diseases namely; malonic aciduria (MA) (1 case), methylmalonic aciduria (MMA) (6 cases), ethylmalonic aciduria (EMA) (4 cases), Canavan’s disease (CD) (1 case), Ornithine carbamoyltransferase deficiency (OCTD) (1 case), classical galactosemia (GAL) (3 cases), homocystinuria (HCY) (2 cases) and Zellweger Syndrome (ZS) (1 case). The above disorders were not appropriately detected by routine MS/MS screening. The concentrations of the diagnostic biomarkers of these disorders were accurately measured and were found to be markedly elevated compared to control samples. The obtained results proved that the described labeled internal standards LC-MS/MS method is a powerful and complementary diagnostic technique to routine MS/MS. The method permits specific detection and quantitation of the diagnostic biomarkers of IMDs in sick infants. The technique is simple and reliable for a rapid differential diagnosis of the metabolic disorders and can be tailored according to physician’s requests.