About this trial
Urea cycle disorders (UCD) are a group of rare inherited metabolism disorders. Infants and children with UCD commonly experience episodes of vomiting, lethargy, and coma. The purpose of this study is to perform a long-term analysis of a large group of individuals with various UCDs. The study will focus on the natural history, disease progression, treatment, and outcome of individuals with UCD.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of NAGS deficiency, defined as the detection of a pathogenic mutation, and/or decreased (less than 20 % of control) NAGS enzyme activity in liver ,and/or hyperammonemia and first degree relative meets at least one of the criteria for NAGS deficiency
Diagnosis of CPS I deficiency, defined as decreased (less than 20 % of control) CPS I enzyme activity in liver, and/or an identified pathogenic mutation, and/or hyperammonemia and first degree relative meets at least one of the criteria for CPS I deficiency
Diagnosis of OTC deficiency, defined as the identification of a pathogenic mutation, and/or less than 20% of control of OTC activity in the liver, and/or elevated urinary orotate (greater than 20 uM/mM) in a random urine sample or after allopurinol challenge test, and/or hyperammonemia and first degree relative meets at least one of the criteria for OTC deficiency
Diagnosis of AS deficiency (Citrullinemia), defined as a greater than or equal to 10-fold elevation of citrulline in plasma, and/or decreased AS enzyme activity in cultured skin fibroblasts or other appropriate tissue, and/or identification of a pathogenic mutation in the AS gene, and/or hyperammonemia and first degree relative meets at least one of the criteria for AS Deficiency
Disqualifiers
Hyperammonemia caused by an organic academia, lysinuric protein intolerance, mitochondrial disorder, congenital lactic academia, fatty acid oxidation defects, or primary liver disease
Rare and unrelated comorbidities (e.g., Down's syndrome, intraventricular hemorrhage in the newborn period, and extreme prematurity)
Trial population
Enrollment goal: 1,100 participants
Trial design
Cohort
Prospective
Treatments tested in this trial
Not listed
Trial groups
Trial outcomes
Primary outcomes
Prevalence of specific morbid indicators of disease severity
hyperammonemia, developmental disabilities, long-term renal and hepatic effects, and case-fatality associated with the various forms of UCD
Relationship between various biomarkers and disease severity and progression
correlation between glutamine, ammonia, liver function (biomarkers) and severity scale and IQ in terms of outcome
Safety and efficacy of currently used and new UCD therapies
Interim events related to treatments (drugs, diet or liver transplant)
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Andrea Gropman
Lead sponsor
Children's National Research Institute
Sponsor institution
National Center for Research Resources (NCRR)
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
Rare Diseases Clinical Research Network
Collaborator