Ornithine transcarbamylase deficiency with persistent abnormality in cerebral glutamate metabolism in adults.

PURPOSE To determine cerebral glutamate turnover rate in partial-ornithine transcarbamylase deficiency (OTCD) patients by using carbon 13 ((13)C) magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS The study was performed with approval of the institutional review board, in compliance with HIPAA regulations, and with written informed consent of the subjects. MR imaging, hydrogen 1 ((1)H) MR spectroscopy, and (13)C MR spectroscopy were performed at 1.5 T in 10 subjects, six patients with OTCD and four healthy control subjects, who were in stable condition. Each received intravenous (13)C-glucose (0.2 g/kg), C1 or C2 position, as a 15-minute bolus. Cerebral metabolites were determined with proton decoupling in a parieto-occipital region (n = 9) and without proton decoupling in a frontal region (n = 1) during 60-120 minutes. RESULTS Uptake and removal of cerebral glucose ([1-(13)C]-glucose or [2-(13)C]-glucose) were comparable in healthy control subjects and subjects with OTCD (P = .1). Glucose C1 was metabolized to glutamate C4 and glucose C2 was metabolized to glutamate C5 at comparable rates, both of which were significantly reduced in OTCD (combined, P = .04). No significant differences in glutamine formation were found in subjects with OTCD (P = .1). [2-(13)C]-glucose and its metabolic products were observed in anterior cingulate gyrus without proton decoupling in one subject with OTCD. CONCLUSION Treatments that improve cerebral glucose metabolism and glutamate neurotransmission may improve neurologic outcome in patients with OTCD, in whom prevention and treatment of hyperammonemic episodes appear to be insufficient.