N-acetylated metabolites in urine:: Proton nuclear magnetic resonance spectroscopic study on patients with inborn errors of metabolism

Background: There is no comprehensive analytical technique to analyze N-acetylated metabolites in urine. Many of these compounds are, involved in inborn errors of metabolism. In the present study, we examined the potential of proton nuclear magnetic resonance (H-1-NMR) spectroscopy as a tool to identify and quantify N-acetylated metabolites in urine of patients with various inborn errors of metabolism. Methods: We performed 1H-NMR spectroscopy on a 500 MHz spectrometer. Using a combination of one- and two-dimensional correlation spectroscopy (COSY) H-1-NMR spectra, we were able to assign and quantify resonances of characteristic N-acetylated compounds products in urine of patients with 13 inborn errors of metabolism. Results: The disease-specific N-acetylated metabolites were excreted at concentrations >100 mumol/mmol of creatinine in the patients' urine. In control urine samples, the concentration of individual N-acetyl-containing compounds was <40 mumol/mmol of creatinine. The combination of one- and two-dimensional COSY NMR spectroscopy led to the correct diagnosis of nine different inborn errors of metabolism. No abnormalities were observed in the spectra of urine from patients with Gm,or G(M2)-gangliosidosis. We also determined the H-1-NMR characteristics of N-acetylated metabolites that may be relevant to human metabolism. Conclusion: H-1-NMR spectroscopy may be used to identify and quantify N-acetylated metabolites of diagnostic importance for the field of inborn errors of metabolism. (C) 2004 American Association for Clinical Chemistry.