Investigation of Brain Nitrogen in Partial Ornithine Transcarbamylase Deficiency (OTCD) Using 1 H MRS, DTI, and fMRI

The overall goal of this project is to characterize metabolic, structural and cognitive
changes in OTCD using 1H MRS, DTI, volumetric averaging and fMRI with cognitive testing of
executive function measures to validate biomarkers for the effect of HA and its treatment on
the brain.

We will measure gln and mI in blood and brain (using 1H MRS) in affected participants, and
mI in brain in controls, fractional anisotropy as a measure of white matter microstructural
damage (by DTI) and brain activation pathways alterations with tasks probing working memory
(fMRI). As a secondary outcome measure, we will correlate the findings from neuroimaging
with cognitive functioning. This protocol is based on our previous 5104 and now includes
children to evaluate the age and stage of disease on these indices in a cohort that is
undergoing important developmental events against an age matched typically developing
cohort.

Inclusion Criteria:

Subject inclusion criteria:

1. Patients with OTCD;

2. Age range: 7-60 years

3. Able to undergo neuroimaging safely (i.e. without presence of ferromagnetic devices)

4. Subject has a documented full scale IQ > 70

Control participant inclusion criteria:

1. Healthy males and females without metabolic disease aged 7-60 years

2. Subject has a documented full scale IQ > 70

Exclusion Criteria:

Subject exclusion criteria:

1. Mental retardation (i.e., Full Scale IQ< 70)

2. Age range <7 or >60 years

3. Presence of ferromagnetic device(s) that preclude safe imaging

4. Pregnant female

Control exclusion criteria:

1. Subjects with a documented history of an intellectual deficit (i.e., Full Scale IQ<
70)

2. Age range <7 or >60 years

3. Presence of ferromagnetic device(s) that preclude safe imaging

4. Pregnant female