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 (C-13) 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 (H-1) MR spectroscopy, and C-13 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 C-13-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-C-13]-glucose or [2-C-13]-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-C-13]-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.