TY - JOUR
T1 - Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder
AU - UCD Consortium
AU - Lee, Brendan
AU - Diaz, George A.
AU - Rhead, William
AU - Lichter-Konecki, Uta
AU - Feigenbaum, Annette
AU - Berry, Susan A.
AU - Le Mons, Cindy
AU - Bartley, James A.
AU - Longo, Nicola
AU - Nagamani, Sandesh C.
AU - Berquist, William
AU - Gallagher, Renata
AU - Bartholomew, Dennis
AU - Harding, Cary O.
AU - Korson, Mark S.
AU - McCandless, Shawn E.
AU - Smith, Wendy
AU - Cederbaum, Stephen
AU - Wong, Derek
AU - Merritt, J. Lawrence
AU - Schulze, Andreas
AU - Vockley, Gerard
AU - Kronn, David
AU - Zori, Roberto
AU - Summar, Marshall
AU - Milikien, Douglas A.
AU - Marino, Miguel
AU - Coakley, Dion F.
AU - Mokhtarani, Masoud
AU - Scharschmidt, Bruce F.
AU - Batshaw, Mark L.
AU - Tuchman, Men Del
AU - Baumgartner, Matthias R.
AU - Hoffmann, Georg
AU - Kerr, Douglas S.
AU - Seashore, Margretta R.
AU - Stricker, Tamar
AU - Waisbren, Susan
AU - Yudoff, Mark
N1 - Publisher Copyright:
© 2015 American College of Medical Genetics and Genomics.
PY - 2015/7/2
Y1 - 2015/7/2
N2 - 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.Genet Med 17 7, 561-568.
AB - 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.Genet Med 17 7, 561-568.
KW - RAVICTI
KW - glycerol phenylbutyrate
KW - hyperammonemia
KW - sodium phenylbutyrate
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U2 - 10.1038/gim.2014.148
DO - 10.1038/gim.2014.148
M3 - Article
C2 - 25503497
AN - SCOPUS:84942804923
SN - 1098-3600
VL - 17
SP - 561
EP - 568
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 7
ER -