Gas chromatographic-mass spectrometric analysis of N-acetylated amino acids: the first case of aminoacylase I deficiency.

During the metabolic work-up of a patient presenting with neonatal convulsions, we consistently observed the presence of unusual peaks in the gas chromatographic-mass spectrometric analysis of urinary organic acids. The gas chromatographic-mass spectrometric characteristics of the unusual peaks suggested that they corresponded to derivatives of N-acetylated amino acids. The tentative identification was confirmed by the identity of retention times and mass spectra of the trimethylsilyl derivatives of the authentic compounds. We describe our observations that led to the identification of the various N-acetylated amino acids in this first patient with a confirmed deficiency of aminoacylase I, an enzyme involved in the cytosolic degradation of N-terminally modified proteins. The potential and limitations of urinary organic acid analysis for the detection of N-acetylated amino acids was further studied using pure compounds. In addition, we provide mass spectral data for 37 trimethylsilyl derivatives from 17 N-acetylated amino acids, most of which have not been reported previously. Our data provide valuable information that will help the clinical laboratorians who are responsible for organic acid analysis to recognize this new condition and could aid its detection in other patients.