Neurologic Injuries in Adults With Urea Cycle Disorders

This study has been completed.
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
Children's Research Institute Identifier:
First received: May 11, 2007
Last updated: October 15, 2014
Last verified: October 2014

Urea cycle disorders (UCDs) are a group of rare inherited metabolism disorders. The purpose of this study is to evaluate how UCD-related neurologic injuries affect adults with one of the most common types of UCD.

Brain Diseases, Metabolic, Inborn
Urea Cycle Disorder
Ornithine Transcarbamylase Deficiency

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Assessing Neural Mechanisms of Injury in Inborn Errors of Urea Metabolism Using Structural MRI, Functional MRI, and Magnetic Resonance Spectroscopy

Resource links provided by NLM:

Further study details as provided by Children's Research Institute:

Primary Outcome Measures:
  • Concentration of glutamine and Myoinositol by MRS [ Time Frame: one time measurement ] [ Designated as safety issue: No ]
    concentration based on area under curve on 1H MRS and quantitated by LCModel

  • Fractional anisotropy [ Time Frame: one time measurement ] [ Designated as safety issue: No ]
    measure of myelin coherence

  • fMRI activation map [ Time Frame: one time measurement ] [ Designated as safety issue: No ]
    measure of task related activation

Enrollment: 46
Study Start Date: March 2007
Study Completion Date: July 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD
Healthy males or females without known medical or metabolic disorder (control group)

Detailed Description:

UCDs are a group of rare genetic diseases that affect how protein is broken down in the body. The cause of UCDs is a deficiency in one of eight enzymes responsible for removing ammonia, a waste product of protein metabolism, from the bloodstream. Normally, ammonia is converted into urea and then removed from the body in the form of urine. However, in people with UCDs, ammonia accumulates unchecked and is not removed from the body. Toxic levels of ammonia can build up and cause irreversible neurologic damage that can affect metabolism, cognition, sensation, and movement. This study will focus on the most common enzyme disorder among UCDs, ornithine transcarbamylase deficiency (OTCD), a disorder inherited from mothers. Using different types of magnetic resonance imaging (MRI), this study will evaluate how UCD-related neurologic injuries affect metabolism, cognition, sensation, and movement in adults with OTCD.

Participants in this study will attend an initial study visit that will include a review of medical history, current symptoms, impairments, and diet history; urine and blood collection; a physical exam; a full neurological exam; and cognitive and motor testing. During this visit, participants will undergo imaging studies and additional cognitive and motor testing over a 2- to 3-day period. This will include standard MRI studies and four sessions consisting of functional MRI (fMRI), diffusion tensor imaging, and 1H magnetic resonance spectroscopy. For the fMRI study, participants perform various motor and behavioral tasks while in the imaging scanner. Magnetic resonance spectroscopy (MRS) is used to study and evaluate the chemical makeup of specific brain areas. Diffusion tensor imaging is used to assess myelination of major brain pathways and their alteration in disease states. This study will involve one-time participation. There will be no follow-up visits for this study.


Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Female carriers of ornithine transcarbamylase deficiency (OTCD) or males with late onset presentation of OTCD


Inclusion Criteria for Participants with OTCD:

  • Diagnosis of OTCD or heterozygote state of OTCD by metabolic or molecular means. Female participants must be clinically stable and heterozygous for OTCD. Male participants must be hemizygous for late onset OTCD.

Inclusion Criteria for Healthy Controls:

  • No known medical or metabolic disorder

Inclusion Criteria for All Participants:

  • IQ of at least 80
  • Willing to travel to study site
  • English-speaking
  • Age between 18 and 60 years

Exclusion Criteria for All Participants:

  • Currently being treated for an acute illness
  • History of neuropsychiatric drug use
  • Unable to undergo MRI scanning without being sedated
  • Unable to participate in neurocognitive and/or motor testing
  • Metal device in body that might interfere with MRI scanning
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00472732

United States, District of Columbia
George Washington University School of Medicine
Washington, District of Columbia, United States, 20037
Georgetown University
Washington, District of Columbia, United States, 20057
Sponsors and Collaborators
Children's Research Institute
Rare Diseases Clinical Research Network
Study Chair: Andrea Gropman, MD Children's Research Institute
  More Information

Responsible Party: Children's Research Institute Identifier: NCT00472732     History of Changes
Other Study ID Numbers: RDCRN 5104, U54RR019453
Study First Received: May 11, 2007
Last Updated: October 15, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Research Institute:
Urea Metabolism
Inborn Errors

Additional relevant MeSH terms:
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Metabolic Diseases
Ornithine Carbamoyltransferase Deficiency Disease
Urea Cycle Disorders, Inborn
Amino Acid Metabolism, Inborn Errors
Central Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Metabolism, Inborn Errors
Nervous System Diseases processed this record on May 21, 2015