Carbamyl Phosphate Synthetase Deficiency, Inborn Errors of Metabolism, Methylmalonic Acidemia, Propionic Acidemia, Urea Cycle Disorders, Inborn
Conditions
Keywords
Ureagenesis, Urea cycle, Inborn errors of metabolism
Brief summary
Hyperammonemia, which can cause brain damage, occurs in many different kinds of inborn errors of metabolism. The investigators propose to determine if short-term (3 day) treatment with N-carbamylglutamate can diminish hyperammonemia by enhancing ureagenesis in these patients. The investigators propose here a short-term (3 day) trial. If it succeeds, the investigators would consider more extensive long-term studies of the drug.
Detailed description
* To determine whether brief (3 day) treatment with N-carbamylglutamate can improve ureagenesis in adult healthy controls and patients with the following inborn errors of metabolism: N-acetylglutamate synthetase deficiency, propionic acidemia, methylmalonic acidemia, carbamylphosphate synthase deficiency, ornithine transcarbamylase deficiency and the syndrome of hyperammonemia, hypoglycemia and hyperinsulinemia (HHH Syndrome). * To determine if such treatment improves other indicators of abnormal nitrogen metabolism such as elevated blood levels of glutamine, glycine and alanine.
Interventions
N-carbamylglutamate: 200 mg/kg/day for 3 days, divided into 4 daily oral doses
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Hospital of Philadelphia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Age range: males or females, ages 3 years - 70 years * Condition(s): N-acetylglutamate synthetase deficiency, propionic acidemia, methylmalonic acidemia, carbamylphosphate synthase deficiency, ornithine transcarbamylase deficiency and the syndrome of hyperammonemia, hypoglycemia and hyperinsulinemia. * In addition, healthy volunteers will be studied (ages 18 years - 50 years).
Exclusion criteria
* Acutely ill on day of study (fever, evidence of hyperammonemia - ataxia, worsening obtundation, focal neurologic signs, seizures, increased intracranial pressure, vomiting, signs of acute respiratory or enteric illness, headache, confusion, disorientation, acute personality change). * Girls 11 years of age must have a negative urine/serum pregnancy test within 1 week prior to testing unless having a menstrual period during week of test * Lactating females * Hyperammonemia probably refractory to N-carbamylglutamate: other urea cycle disorders (UCD), lysinuric protein intolerance, mitochondrial disorders, congenital lactic acidemia, fatty acid oxidation defects or primary liver disease. * Amount of blood necessary for study exceeds safe limits. * Any investigational drug use within 30 days prior to enrollment. * Parents/guardians or subjects who, in the opinion of the PI, may be non-compliant with study schedules or procedures. * Subjects who do not meet all the enrollment criteria may not be enrolled. Any violations of these criteria will be reported in accordance with Institutional Review Board (IRB) Policies and Procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of ureagenesis | 3 days | Goal is to determine whether a 3 day trial of N-carbamylglutamate increases ureagenesis in patients with urea cycle defects and other inborn errors of metabolism. |
Outcome results
None listed