Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder.

Abstract

PURPOSE:

The aim of this study was to examine predictors of ammonia exposure and hyperammonemic crises in patients with urea cycle disorders.

METHODS:

The relationships between fasting ammonia, daily ammonia exposure, and hyperammonemic crises were analyzed in >100 patients with urea cycle disorders.

RESULTS:

Fasting ammonia correlated strongly with daily ammonia exposure (r = 0.764; P < 0.001). For patients with fasting ammonia concentrations <0.5 upper limit of normal (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, respectively, experienced ≥1 hyperammonemic crisis over 12 months. Time to first hyperammonemic crisis was shorter (P = 0.008) and relative risk (4.5×; P = 0.011) and rate (~5×, P = 0.006) of hyperammonemic crises were 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 old. A 10- or 25-µmol/l increase in ammonia exposure increased the relative risk of a hyperammonemic crisis by 50 and >200% (P < 0.0001), respectively. The relationship between ammonia and hyperammonemic crisis risk seemed to be independent of treatment, age, urea cycle disorder subtype, dietary protein intake, or blood urea nitrogen. Fasting glutamine correlated weakly with daily ammonia exposure assessed as 24-hour area under the curve and was not a significant predictor of hyperammonemic crisis.

CONCLUSION:

Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of hyperammonemic crises, suggesting that patients with urea cycle disorder may benefit from tight ammonia control.

• Authors: Brendan Lee, George A Diaz, William Rhead, Uta Lichter-Konecki, Annette Feigenbaum, Susan A Berry, Cindy Le Mons, James A Bartley, Nicola Longo, Sandesh C Nagamani, William Berquist, Renata Gallagher, Dennis Bartholomew, Cary O Harding, Mark S Korson, Shawn E McCandless, Wendy Smith, Stephen Cederbaum, Derek Wong, J Lawrence Merritt 2nd, Andreas Schulze, Jerry Vockley, Gerard Vockley, David Kronn, Roberto Zori, Marshall Summar, Douglas A Milikien, Miguel Marino, Dion F Coakley, Masoud Mokhtarani, UCD Consortium, Bruce F Scharschmidt
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 17 Issue 7 Pg. 561-8 (Jul 2015) ISSN: 1530-0366 [Electronic] United States
• PMID: 25503497 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamine
• Ammonia

Topics

• Adolescent
• Adult
• Ammonia (blood)
• Child
• Child, Preschool
• Female
• Glutamine (blood)
• Humans
• Hyperammonemia (blood)
• Infant
• Male
• Middle Aged
• Predictive Value of Tests
• Urea Cycle Disorders, Inborn (blood)
• Young Adult