Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders
Oxidative Stress, Inflammation and Acute Decompensation in Urea Cycle Disorders
The primary purpose of the proposed study is to characterize the oxidative stress and
 inflammatory cytokine status in UCD during baseline and decompensated states.
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.
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.