Neurologic Injuries in Adults With Urea Cycle Disorders


Andrea Gropman




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

Study type


Funder types



U54RR019453 (U.S. NIH Grant/Contract)
RDCRN 5104

Details and patient eligibility


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.

Full 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.


46 patients




18 to 60 years old


Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

46 participants in 2 patient groups

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)

Trial contacts and locations



Data sourced from

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