BLOOD AMMONIA AND GLUTAMINE AS PREDICTORS OF HYPERAMMONEMIC CRISES IN UREA CYCLE DISORDER PATIENTS

PURPOSE: To examine predictors of ammonia exposure and hyperammonemic crises (HAC) in patients with urea cycle disorders (UCDs). METHODS: The relationships between fasting ammonia, daily ammonia exposure, and HACs were analyzed in >100 UCD patients. RESULTS: Fasting ammonia correlated strongly with daily ammonia exposure (r=0.764, p<0.001). For patients with fasting ammonia levels <0.5 ULN, 0.5 to <1.0 ULN, and ≥1.0 ULN, the probability of a normal average daily ammonia value was 87%, 60%, and 39%, respectively, and 10.3%, 14.1%, and 37.0% of these patients experienced ≥1 HAC over 12 months. Time to first HAC was shorter (p=0.008) and relative risk (4.5×; p=0.011) and rate (~5×, p=0.006) of HACs higher in patients with fasting ammonia ≥1.0 ULN vs. <0.5ULN; relative risk was even greater (20×; p=0.009) in patients ≥6 years. A 10 or 25 μmol/L increase in ammonia exposure increased the relative risk of a HAC by 50% and >200% (p<0.0001), respectively. The relationship between ammonia and HAC risk appeared independent of treatment, age, UCD subtype, dietary protein intake, or blood urea nitrogen. Fasting glutamine correlated weakly with AUC(0-24) and was not a significant predictor of HACs. CONCLUSIONS: Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of HACs, suggesting that UCD patients may benefit from tight ammonia control.