Genet Med. 2015 Jul;17(7):561-8. doi: 10.1038/gim.2014.148. Epub 2014 Dec 11.

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

Lee B¹, Diaz GA², Rhead W³, Lichter-Konecki U⁴, Feigenbaum A⁵, Berry SA⁶, Le Mons C⁷, Bartley JA⁸, Longo N⁹, Nagamani SC¹⁰, Berquist W¹¹, Gallagher R¹², Bartholomew D¹³, Harding CO¹⁴, Korson MS¹⁵, McCandless SE¹⁶, Smith W¹⁷, Cederbaum S¹⁸, Wong D¹⁸, Merritt JL 2nd¹⁹, Schulze A⁵, Vockley J, Kronn D²¹, Zori R²², Summar M⁴, Milikien DA²³, Marino M¹⁵, Coakley DF²⁴, Mokhtarani M²⁴; UCD Consortium, Scharschmidt BF²⁴.

Collaborators (9)

Batshaw ML, Tuchman M, Baumgartner MR, Hoffmann G, Kerr DS, Seashore MR, Stricker T, Waisbren S, Yudoff M.

Author information

1: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
2: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3: The Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
4: Children's National Medical Center, Washington, DC, USA.
5: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
6: University of Minnesota, Minneapolis, Minnesota, USA.
7: National Urea Cycle Disorders Foundation, Pasadena, California, USA.
8: Miller Children's Hospital, Long Beach, California, USA.
9: University of Utah, Salt Lake City, Utah, USA.
10: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
11: Stanford University, Palo Alto, California, USA.
12: Children's Hospital Colorado, Aurora, Colorado, USA.
13: Nationwide Children's Hospital, Columbus, Ohio, USA.
14: Oregon Health & Science University, Portland, Oregon, USA.
15: Tufts Medical Center, Boston, Massachusetts, USA.
16: University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
17: Maine Medical Center, Portland, Maine, USA.
18: University of California, Los Angeles, Los Angeles, California, USA.
19: University of Washington, Seattle, Washington, USA.
20: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
21: Westchester Medical Center, Westchester, New York, USA.
22: University of Florida, Gainesville, Florida, USA.
23: Accudata Solutions, Lafayette, California, USA.
24: Hyperion Therapeutics, Brisbane, California, USA.

Erratum in

ERRATUM: Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. [Genet Med. 2015]

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.