Journal
MOLECULAR GENETICS AND METABOLISM
Volume 94, Issue 1, Pages 52-60Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2007.12.008
Keywords
ammonia; urea cycle; H-1 magnetic resonance spectroscopy (MRS); myoinositol; ornithine transcarbamylase deficiency (OTCD); stable isotopes
Funding
- NCRR NIH HHS [K12 RR017613-03, M01 RR020359, K12 RR017613, M01 RR020359-01, U54 RR019453, K12RR17613, 1M01RR020359-010058] Funding Source: Medline
- NICHD NIH HHS [U54 HD061221, P30 HD040677] Funding Source: Medline
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We used H-1 MRS to evaluate brain metabolic differences in sisters with partial ornithine transcarbamylase deficiency (OTCD) who had discordant clinical symptoms and urea synthetic capabilities to assess whether a brain biomarker of partial OTCD correlated with urea synthetic ability and clinical severity. We performed single voxel 3.0T H-1 MRS in two adult sisters with partial OTCD, one symptomatic and one asymptomatic, in a stable medical state and compared it to one age matched adult control, as well as data collected on an additional 13 subjects with partial OTCD and 12 controls. Data from voxels placed in frontal and parietal white matter (FWM, PWM), posterior cingulate gray matter (PCGM), and thalamus (tha), were corrected for partial volume and analyzed using LCModel. All three subjects as well as the symptomatic mother of the two sisters, had neurocognitive testing, plasma ammonia levels, plasma amino acid, and urine organic acid analysis. Previous urea synthetic capabilities had been measured by stable isotope analysis. We found IQ scores to be inversely related to symptoms. Decreased myoinositol (mI) identified OTCD subjects, even the sister who is asymptomatic, in the posterior parietal white matter and frontal white matter. Brain metabolism is impaired in partial OTCD. Abnormal metabolism in apparently asymptomatic OTCD females may provide an explanation for neurocognitive impairments previously reported. The concentration of mI seen on H-1 MRS in PWM and FWM in this family could be used to deduce clinical symptomatology and may serve as a non-invasive marker of brain liability in OTCD. (c) 2007 Elsevier Inc. All rights reserved.
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