Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)
| Status: | Completed |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/16/2015 |
| Start Date: | December 2012 |
| End Date: | September 2014 |
| Contact: | Mary Mullins, BSN |
| Email: | mullins@bcm.edu |
| Phone: | (832)822-4263 |
RDCRN 5110, Nitric Oxide Flux and Ureagenesis in Argininosuccinate Synthetase Deficiency (ASSD)(Citrullinemia I)(Version 24Feb12, NIH Approved 4/5/2012)
The urea cycle consists of a series of chemical reactions through which the body converts
toxic waste- nitrogen into a substance called urea that can be disposed of easily. While
disposal of nitrogen is the major function of the urea cycle, recent research has shown that
some enzymes of the urea cycle are also important for the production of nitric oxide. Nitric
oxide is an important chemical that has many functions in the human body including
regulation of blood pressure. Through this study, the investigators will study the
production of nitric oxide in subjects with citrullinemia type 1 by administering stable
isotopes to these subjects. Stable isotopes are harmless compounds that can be used to track
and measure the production of specific compounds in the human body. The overall goal of this
study is to understand if citrullinemia patients have a deficiency of nitric oxide
production. This knowledge may have an impact on the treatment of patients with
citrullinemia.
toxic waste- nitrogen into a substance called urea that can be disposed of easily. While
disposal of nitrogen is the major function of the urea cycle, recent research has shown that
some enzymes of the urea cycle are also important for the production of nitric oxide. Nitric
oxide is an important chemical that has many functions in the human body including
regulation of blood pressure. Through this study, the investigators will study the
production of nitric oxide in subjects with citrullinemia type 1 by administering stable
isotopes to these subjects. Stable isotopes are harmless compounds that can be used to track
and measure the production of specific compounds in the human body. The overall goal of this
study is to understand if citrullinemia patients have a deficiency of nitric oxide
production. This knowledge may have an impact on the treatment of patients with
citrullinemia.
This is an interventional, case control study to investigate the production of nitric oxide
in patients with citrullinemia type I. Through the infusion of isotopes [15N2-ureido]
arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and
[15N][18O3] potassium nitrate, the flux of citrulline and nitrate through the urea cycle
pathway will be measured in conjunction with an independent measure of total plasma arginine
flux. This will be informative in dissecting the contributions of de novo production of
arginine vs. exogenous contribution of arginine into total body NO flux. Total body urea
production will be measured by the isotopic dilution of constantly infused [18O][13C]urea.
These flux measurements will be correlated with the level of residual enzyme activity and
clinical phenotype in these citrullinemia patients. The investigators plan to enroll three
patients with citrullinemia.
Three unaffected control subjects will also be studied.
in patients with citrullinemia type I. Through the infusion of isotopes [15N2-ureido]
arginine, [5-13C,4, 4, 5, 5-D4] citrulline, [15N]citrulline, 15N sodium nitrate and
[15N][18O3] potassium nitrate, the flux of citrulline and nitrate through the urea cycle
pathway will be measured in conjunction with an independent measure of total plasma arginine
flux. This will be informative in dissecting the contributions of de novo production of
arginine vs. exogenous contribution of arginine into total body NO flux. Total body urea
production will be measured by the isotopic dilution of constantly infused [18O][13C]urea.
These flux measurements will be correlated with the level of residual enzyme activity and
clinical phenotype in these citrullinemia patients. The investigators plan to enroll three
patients with citrullinemia.
Three unaffected control subjects will also be studied.
Inclusion Criteria:
- Participants must be adults (18 years and older) with confirmed diagnosis of
Argininosuccinate Synthetase Deficiency (ASSD) (Citrullinemia I) who are able to
perform study procedures.
- Diagnosis of citrullinemia I must be confirmed by a >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 pathogenic mutation in the AS gene.
- Subject must be able to take oral or G-tube medication and have a history of adequate
compliance of diet and treatment.
- If a woman of child bearing potential and sexually active, participant agrees to use
an acceptable method of birth control.
- Most recent serum creatinine level must be less than or equal to 1.5 mg/dl. Serum
creatinine measurement may be performed at the subject's local laboratory, but must
have been obtained within one year of enrollment.
- Participant agrees to travel to Baylor College of Medicine for the study.
- Control subjects must be over eighteen years of age with no chronic or acute health
issues.
Exclusion Criteria:
- Pregnancy, current acute illness and current hyperammonemic episode.
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