beta-ureidopropionase deficiency: A novel inborn error of metabolism discovered using NMR spectroscopy on urine

In this work, NMR investigations that led to the discovery of a new inborn error of metabolism, beta -ureidopropionase (UP) deficiency, are reported. 1D H-1-NMR experiments were performed using a patient's urine. 3-Ureidoprop ionic acid was observed in elevated concentrations in the urine spectrum. A 1D H-1-H-1 total correlation spectroscopy (TOCSY) and two heteronuclear 2D NMR techniques (heteronuclear multiple bond correlation (HMBC) and heteron uclear single-quantum correlation (HSQC)) were used to identify the molecul ar structure of the compound that caused an unknown doublet resonance at 1. 13 ppm. Combining the information from the various NMR spectra, this resona nce could be assigned to 3-ureidoisobutyric acid. These observations sugges ted a deficiency of UP. With 1D H-1-NMR spectroscopy, UP deficiency can be easily diagnosed. The H-1-NMR spectrum can also be used to diagnose patient s suffering from other inborn errors of metabolism in the pyrimidine degrad ation pathway. (C) 2001 Wiley-Liss, Inc.