Investigation of urea cycle enzyme disorders by 1H-NMR spectroscopy

High resolution proton nuclear magnetic resonance spectroscopy (1H-NMR) has been used to study patients with inborn errors of the urea cycle to evaluate further the diagnostic potential of this technique. The 1H-NMR metabolic profile from the urine of patients with citrullinaemia and argininosuccinic aciduria consistently demonstrated the presence of the diagnostic metabolites citrulline, N-acetylcitrulline and argininosuccinate, respectively. The profile from the urine of patients with ornithine carbamoyl transferase deficiency, is potentially diagnostic, but orotate was only detected in samples from three out of four patients. The characteristic fingerprint that each of the metabolites produces is unlike that of any other we have seen, including analogues of the metabolites which are structurally very similar such as arginine, ornithine and aspartate. The level of excretion of the metabolites from the patients with citrullinaemia and argininosuccinic aciduria has been well within the range of NMR detection.