Longitudinal Study of Urea Cycle Disorders

Individuals with Urea Cycle Disorders (UCD) cannot remove ammonia, a waste product, from the blood. The purpose of this study is to conduct a longitudinal investigation of the natural history, morbidity, and mortality in people with UCD. This study will look at how people with a UCD grow and develop over time and how often they get sick.

The research questions are:

1. What is the prevalence of specific morbid indicators of disease severity, including hyperammonemia, developmental disabilities, and various long-term kidney and liver effects? What is the fatality rate associated with the various forms of UCD?
2. What are the correlations between various biomarkers and disease severity and progression?
3. What is the safety and efficacy of currently used and new UCD therapies?

This is a longitudinal study of individuals with urea cycle disorders. Those participating in this study will be evaluated every three to twelve months, depending age and time of diagnosis. Participants two years of age and younger that were diagnosed with UCD within the first four weeks of life will be evaluated every three months. Those who are over two years of age or were diagnosed after four weeks of age will be evaluated every six months. Participants older than 18 years of age will be evaluated once every year.

• Study Weblinks:
  • Rare Disease Clinical Research Network
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
• Total number of consented subjects: 542
• Subject Sample Telemetry Report (SSTR)

Inclusion criteria: Confirmed diagnosis of one of the eight UCDs or UCD diagnosis highly likely/pending.

The eight disorders are:

Exclusion Criteria: We will exclude cases of hyperammonemia caused by an organic acidemia, lysinuric protein intolerance, mitochondrial disorders, congenital lactic acidemia, fatty acid oxidation defects and primary liver disease. We will also exclude individuals with rare and unrelated serious comorbidities, e.g., Down syndrome, intraventricular hemorrhage in the newborn period, and extreme low birth weight (>1,500 grams).

• Primary Phenotype: Urea Cycle Disorders, Inborn

• BioProject
• PubMed
• MeSH
• PMC

• Study Chairs
  • Mark Batshaw, MD. Children's National Medical Center, Washington, DC, USA.
  • Mendal Tuchman, MD. Children's National Medical Center, Washington, DC, USA.
• Participating Site, Principal Investigators
  • Uta Lichter-Konecki, MD. Children's National Medical Center, Washington, DC, USA.
  • Marc Yudkoff, MD. Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Brendan Lee, MD, PhD. Baylor College of Medicine, Houston, TX, USA.
  • Derek Wong, MD. University of California, Los Angeles, CA, USA.
  • George Diaz, MD, PhD. Mount Sinai School of Medicine, New York, NY, USA.
  • Douglas Kerr, MD, PhD. University Hospitals of Cleveland/Rainbow Babies and Children's Hospital, Cleveland, OH, USA.
  • Matthias Baumgartner, MD. University of Children's Hospital Zurich, Steinwiesstr.
  • Andreas Schulze, MD. The Hospital for Sick Children, Toronto, Ontario, Canada.
  • J. Lawrence Merritt, II, MD. Seattle Children's Hospital, Seattle, WA, USA.
  • Cary Harding, MD. Oregon Health and Science University, Portland, OR, USA.
  • Renata C. Gallagher, MD, PhD. The Children's Hospital, Aurora, CO, USA.
  • Susan Waisbren, PhD. New England Center Children's Hospital, Boston, MA, USA.
  • Susan A. Berry, MD. University of Minnesota Amplatz Children's Hospital, Minneapolis, MN USA.
  • Georg F. Hoffmann, MD. University of Heidelberg Centre for Pediatric and Adolescent Medicine, Heidelberg, GERMANY.
  • Jeffrey Krischer, PhD. Data Management and Coordinating Center University of South Florida, FL USA.
• Current Funding Sources
  • U54-HD061221-06. National Institutes of Health, Bethesda, MD, USA.