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Study Description

This project studies cognitive and motor dysfunction in adult and pediatric patients who are female carriers of ornithine transcarbamylase deficiency (OTCD) or are males with late onset presentation (outside of the newborn period) of OTCD, utilizing state of the art MRI (magnetic resonance imaging), a non-invasive technique. This project seeks to improve our understanding of the underlying neural mechanisms that contribute to metabolic, cognitive, sensory and motor abnormalities in urea cycle disorders, which although individually rare, collectively constitute a major cause of neonatal encephalopathy, leading to significant morbidity and mortality.

As a result of this study, a greater understanding of the anatomic, cognitive, motor, and biochemical underpinnings of neurologic damage attributable to this metabolic disorder will be gained. Experimental approaches will combine sensory, cognitive and motor testing with structural, functional and molecular magnetic resonance imaging to study symptomatic and asymptomatic heterozygous female carriers of X-linked ornithine transcarbamylase deficiency (OTCD), and late onset hemizygous males.

Participants to be included in the studies will range from ages 7-60 years and will be compared to an age-matched typically developed (TD) comparison group.

For our research, we use anatomic MRI, functional Magnetic Resonance Imaging (fMRI), and magnetic resonance spectroscopy (MRS) to monitor brain activity. The technique of fMRI provides detailed maps of the brain areas underlying human mental activities. By using fMRI, we are able to observe how the brain is functioning while a person is performing a specific task, such as reading. We can not only observe differences in the structure of the brain, but can also measure differences in brain function and activity as well. This information will ultimately be used to provide a basis for designing more effective interventions and methods for early identification of learning disabilities in patients with OTCD and related disorders. We will also use MRS to study various brain chemicals such as glutamine using the non-invasive MRI imaging techniques.

  • Study Types: Observational, Cohort, Case-Control
  • Number of study subjects that have individual level data available through Authorized Access: 12

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion 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

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 participant inclusion criteria:

  1. Healthy males and females without metabolic disease aged 7-60 years
  2. Subject has a documented full scale IQ > 70

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

Study History

  • Study Activated September 12, 2010
  • First Accrual October 4, 2010
  • Last DSMB review December 1, 2014
  • Next DSMB review scheduled for January 12, 2016
  • Study Closed to Accrual in data analysis on November 18, 2014

Selected publications
Diseases/Traits Related to Study (MESH terms)
Links to Related Resources
Authorized Data Access Requests
Study Attribution