Neurologic Injuries in Adults With Urea Cycle Disorders

Brief Title

Neurologic Injuries in Adults With Urea Cycle Disorders

Official Title

Assessing Neural Mechanisms of Injury in Inborn Errors of Urea Metabolism Using Structural MRI, Functional MRI, and Magnetic Resonance Spectroscopy

Brief Summary

      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.

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

      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.

Study Type


Primary Outcome

Concentration of Glutamine and Myoinositol by MRS


Brain Diseases, Metabolic, Inborn

Study Arms / Comparison Groups

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


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

March 2007

Completion Date

July 2010

Primary Completion Date

July 2009

Eligibility Criteria

        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




18 Years - 60 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Andrea Gropman, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID

RDCRN 5104

Secondary IDs


Responsible Party


Study Sponsor

Andrea Gropman


 Office of Rare Diseases (ORD)

Study Sponsor

Andrea Gropman, MD, Study Chair, Children's National Research Institute

Verification Date

May 2015