Jump to: Authorized Access | Attribution | Authorized Requests

Study Description

Urea cycle disorders represent a group of rare inborn errors of metabolism that lead to accumulation of ammonia, a toxic product of protein metabolism. Individuals with urea cycle disorders cannot metabolize the ammonia that accumulates due to enzyme deficiency. The symptoms of these disorders may present at birth, childhood or adulthood (milder deficiencies). There are currently eight enzyme deficiencies that constitute the range of inborn errors of ureagenesis. This project will focus on the most common enzyme disorder of the urea cycle, ornithine transcarbamylase deficiency, inherited as an X-linked trait.

This project will study cognitive and motor dysfunction in patients who are female carriers of ornithine transcarbamylase deficiency (OTCD) or are males with late onset presentation 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 18-60 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 Weblinks:
  • Study Type:
    • Case-Control
  • Number of study subjects that have individual-level data available through Authorized Access:
Authorized Access
Publicly Available Data (Public ftp)

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

Study Inclusion/Exclusion Criteria

Inclusion Criteria (Cases):

  • Clinically stable (not acutely ill at the time of the study), heterozygous female with OTCD or hemizygous male with late onset OTCD.
  • Female of child bearing potential who is sexually active agrees to a urine pregnancy test.
  • Age range between 18 and 60 years old.
  • Confirmed diagnosis of OTCD or heterozygote state by metabolic or molecular means.
  • Native English speaker (fMRI language tasks standardized for native English speakers).
  • IQ of at least 80.
  • Able to undergo MRI scanning without the use of sedation.
  • Absence of significant history of neuropsychiatric drug use.
  • Willing to travel to Georgetown University and participate in 2-3 days of neuroimaging at CFMI.
  • Ability to be scanned safely (i.e., without presence of metallic device-see exclusions below).

Exclusion Criteria (Cases):

  • Participant is pregnant or nursing
  • Participant is currently being treated for an acute illness.
  • Unable to comply with neurocognitive and/or motor testing.
  • Participant with contraindication to MRI (i.e. presence of a metal device that may concentrate radio frequency fields per radiology guidelines for MRI studies including pacemakers, cochlear implants, defibrillators, aneurysm clips, iron filings in the eyes, etc.).
  • Participant is younger than 18, or older than 60 years of age.

Inclusion Criteria (Controls):
To be eligible for the study all the inclusion criteria should be met:

  • Healthy male or female without known medical or metabolic disorder.
  • Female of child bearing potential who is sexually active agrees to a urine pregnancy test.
  • Age range between 18 and 60 years old.
  • Native English speaker (fMRI language tasks standardized for native English speakers).
  • IQ of at least 80.
  • Able to undergo MRI scanning without the use of sedation.
  • Absence of significant history of neuropsychiatric drug use.
  • Willing to travel to Georgetown University and participate in 2-3 days of neurocognitive testing and neuroimaging at CFMI.
  • Ability to be scanned safely (i.e. without presence of metallic device-see exclusions below).

Exclusion Criteria (Controls):

  • Participant is pregnant or nursing.
  • Participant is currently being treated for an acute illness.
  • Unable to comply with neurocognitive and/or motor testing.
  • Participant with contraindication to MRI (i.e. presence of a metal device that may concentrate radio frequency fields per radiology guidelines for MRI studies including pacemakers, cochlear implants, defibrillators, aneurysm clips, iron filings in the eyes, etc.).
  • Participant is younger than 18, or older than 60 years of age.

Study History

  • Study Activated March 19, 2007
  • First Accrual March 29, 2007
  • Study Closed to accrual September 1, 2009
  • Study Final Closed April 2, 2013

Selected publications
Diseases/Traits Related to Study (MeSH terms)
Links to Related Resources
Authorized Data Access Requests
See research articles citing use of the data from this study
Study Attribution
Feedback