title: Error analysis in newborn screening: can quotients support the absolute values?
abstract: Newborn screening is performed using modern tandem mass spectrometry, which can simultaneously detect a variety of analytes, including several amino acids and fatty acids. Tandem mass spectrometry measures the diagnostic parameters as absolute concentrations and produces fragments which are used as markers of specific substances. Several prominent quotients can also be derived, which are quotients of two absolute measured concentrations. In this study, we determined the precision of both the absolute concentrations and the derived quotients. First, the measurement error of the absolute concentrations and the measurement error of the ratios were practically determined. Then, the Gaussian theory of error calculation was used. Finally, these errors were compared with one another. The practical analytical accuracies of the quotients were significantly higher (e.g., coefficient of variation (CV) = 5.1% for the phenylalanine to tyrosine (Phe/Tyr) quotient and CV = 5.6% for the Fisher quotient) than the accuracies of the absolute measured concentrations (mean CVs = 12%). According to our results, the ratios are analytically correct and, from an analytical point of view, can support the absolute values in finding the correct diagnosis.
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Justus Liebig University Giessen, Feulgenstr. 12, 35392, Giessen, Germany. borros.arneth@klinchemie.med.uni-giessen.de.
authors.forename: Borros
authors.initials: B
authors.lastname: Arneth
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Justus Liebig University Giessen, Feulgenstr. 12, 35392, Giessen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hintz
mesh_terms: D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000592:standards*; D053719:Tandem Mass Spectrometry / Q000379:methods
keywords: Measurement error; Metabolic pattern; Metabolism; Newborn screening; Tandem mass spectrometry