Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

Study Overview
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Brief Summary
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The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states.

Detailed Description
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Protein turnover is a cyclic process with a net loss of protein in the fasting state and a net gain in the fed state contributing to nitrogen balance. These physiologic processes are impacted during infection; whole-body protein catabolism exceeds protein synthesis, resulting in net loss of whole-body protein. Patients with urea cycle disorders suffer episodes of periodic hyperammonemic crisis, often in association with intercurrent infections. The immediate cause of this decompensation is the increase in endogenous protein catabolism that is the endpoint of a cascade triggered by intercurrent illness. This increase in protein catabolism leads to elevations of serum amino acids and ammonia production, which cannot be eliminated by a dysfunctional urea cycle. It is well known that infectious illnesses play a significant role in precipitating metabolic crises in urea cycle defects, presumably by triggering a cascade of events involving the release of inflammatory cytokines that lead to increased protein catabolism. Cytokines have also been implicated as distant mediators of oxidative stress. However, the correlation between oxidative stress, cytokine levels, and severity of a crisis is currently unclear. The primary purpose of the proposed study is to characterize the oxidative stress and inflammatory cytokine status in UCD during baseline and decompensated states. The investigators will undertake measurements of selected markers of oxidative stress and cytokines in serum and urine during baseline and decompensated states in subjects with UCD in order to establish their prognostic value as biomarkers for disease severity and/or predictors of metabolic decompensation.

Official Title
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Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders

Conditions
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Urea Cycle Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed or highly-likely diagnosis of one of the eight UCDs as established for the Longitudinal Study (5101) (See section 4.2 Inclusion Criteria, Table 4 for diagnostic criteria for patients with UCD) Enrolled in Longitudinal Study of Urea Cycle Disorders (RDCRN UCDC #5101) Exclusion Criteria: UCD patients who have undergone orthotopic liver transplantation Significant chronic medical co-morbidity that might confound the analysis as determined by the site investigators. Significant co-morbidities include but are not limited to: diabetes, liver failure + cirrhosis renal failure cardiac disease chronic inflammatory diseases asthma requiring daily long-term control medications significant respiratory disease.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory values indicating oxidative stress | Laboratory values that indicate oxidative stress include IL-1, IL-2, IL-6, and IL-8. These values will be analyzed as a panel (not individually) comparing baseline values to values during periods of decompensation. | Change from baseline to period of decompensation up to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urea cycle disorders