DEVELOPING A NOVAL CARBON 13 TEST FOR MONITORING UREAGENESIS

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The purpose of this project is to develop an ultra-sensitive stable isotope test that will measure the rate of Ureagenesis in patients with the classical (severe) form of ornithine transcarbamylase deficiency (OTCD) who form urea at a rate that is <5% of that of the control population. At this juncture we will be attempting to develop such a test only in healthy adults. Our underlying hypotheses are: a) We can successfully monitor ureagenesis by measuring the incorporation of H13CO3 into urea; b) The mass spectrometric methods we will use for this purpose will prove so sensitive as to allow the determination of Ureagenesis even if it is <5% of the control value; c) subjects with OTCD will form (13C) urea from H13CO3 at a rate that is significantly less than that of controls; d) The proposed test will be so sensitive that it will permit us even to detect very small (5-10%) changes in the rate of ureagenesis in OTCD patients who receive an adenoviral vector containing a cDNA for the OTC gene. The clinical significance of this project, therefore, will be the development of a clinical test with which we can monitor the efficacy of gene therapy for this inborn error of metabolism.