SCREENING BLOOD SPOTS FOR INBORN-ERRORS OF METABOLISM BY ELECTROSPRAYTANDEM MASS-SPECTROMETRY WITH A MICROPLATE BATCH PROCESS AND A COMPUTER ALGORITHM FOR AUTOMATED FLAGGING OF ABNORMAL PROFILES

Metabolic profiling of amino acids and acylcarnitines from blood spots by automated electrospray tandem mass spectrometry (ESI-MS/MS) is a p owerful diagnostic tool for inborn errors of metabolism. New approache s to sample preparation and data interpretation have helped establish the methodology as a robust, high-throughput neonatal screening method . We introduce an efficient 96-well-microplate batch process for blood -spot sample preparation, with which we can obtain high-quality profil es from 500-1000 samples per day per instrument. A computer-assisted m etabolic profiling algorithm automatically flags abnormal profiles. We selected diagnostic parameters for the algorithm by comparing profile s from patients with known metabolic disorders and those from normal n ewborns. Reference range and cutoff values for the diagnostic paramete rs were established by measuring either metabolite concentrations or p eak ratios of certain metabolite pairs. Rigorous testing of the algori thm demonstrates its outstanding clinical sensitivity in flagging abno rmal profiles and its high cumulative specificity.