Abstract #2: Adults with Ornithine Transcarbamylase Deficiency (OTCD) Demonstrate Persistent Abnormality in Cerebral Glutamate Metabolism

Abstract

Objective 13C MRS to determine cerebral glutamate turnover rate in partial ornithine transcarbamylase deficiency (OTCD). Background Patients with OTCD manifest neuropsychological disorders. Proton magnetic resonance spectroscopy (1H MRS) demonstrates neurochemical abnormalities in OTCD similar to chronic and subclinical hepatic encephalopathy (SCHE) in whom impaired cerebral glucose metabolism and reduced glutamine-glutamate cycling or glutamate neurotransmission rate (GNT) have been observed. We hypothesize impaired GNT may underlie cognitive deficits in OTCD. Design/Methods MRI, 1H MRS and 13C MRS were performed on a clinical GE 1.5 T MR scanner in 6 patients with OTCD and 4 normal controls, imaged in stable condition. Each received i.v. 13C glucose (0.2 g/kg) C1 or C2, as a 15-min bolus. Cerebral metabolites were determined with proton decoupling, in posterior cingulate gyrus (PCG, N = 9) and without proton decoupling, in anterior (N = 1) cingulate gyrus (ACG) over 60–100 minutes. Results 1. Uptake and removal of cerebral glucose (13C-C1 or C2) were comparable in normal controls and subjects with OTCD ( p > 0.1). 2. Glucose C1 was metabolized to glutamate C4 and glucose C2 to glutamate C5 at comparable rates which were significantly reduced in OTCD (combined p p > 0.1). 4. 13C - 2 glucose and its metabolic products were observed in ACG without proton decoupling in a single subject with OTCD. Conclusions/Relevance Reduced GNT secondary to impaired cerebral glucose metabolism was documented in OTCD using 13C MRS of occipital lobe. Feasibility of this measurement in more relevant frontal brain structures was demonstrated. Treatment(s) which improve cerebral glucose metabolism and GNT may improve neurological outcome in OTCD where prevention and treatment of hyperammonemic episodes appears insufficient.