Development, Validation and Application of Tandem Mass Spectrometry for Screening of Inborn Metabolic Disorders in Kuwaiti Infants

Objective: The aim of this work was to develop a specific and validated tandem mass spectrometric (MS/MS) method for screening of amino acidopathies, organic acidurias, urea cycle disorders and fatty acid oxidation defects in Kuwaiti newborns and sick infants. Materials and Methods: A total of 1,520 blood samples were tested for inborn metabolic disorders in Kuwaiti newborns and sick infants. Positive electrospray MS/MS was used to measure diagnostic acylcarnitines and amino acids in blood spots after simple extraction and derivatization procedures. Validation and stability studies were conducted using control blood samples supplemented with known concentrations of the diagnostic amino acids or acylcarnitines. Reference and cutoff levels of the diagnostic metabolites were determined in a group of 500 normal Kuwaiti babies for quantitative evaluation. Results: Of the 1,520 samples, 32 were positive newborn cases and 27 positive symptomatic infants. For the validation studies, the range of relative standard deviation was 2.6–14.7%, whereas the range of the percent deviation from nominal concentrations was –23.0 to +25.0 of the diagnostic metabolites. Stability studies indicated appropriate stability of the diagnostic amino acids and acylcarnitines in dried blood spots stored at 22 ± 1°C and relative humidity of 50–60%. Conclusions: Tandem mass spectrometry can significantly contribute to a newborn screening program as a fast and highly specific diagnostic technique for screening of a broad range of inborn metabolic disorders.