Glutamine and hyperammonemic crises in patients with urea cycle disorders

B. Lee, G. A. Diaz, W. Rhead, U. Lichter-Konecki, A. Feigenbaum, S. A. Berry, C. Le Mons, J. Bartley, N. Longo, S. C. Nagamani, W. Berquist, R. C. Gallagher, Cary Harding, S. E. McCandless, W. Smith, A. Schulze, Miguel Marino, R. Rowell, D. F. Coakley, M. Mokhtarani & 1 others B. F. Scharschmidt

Research output: Contribution to journalArticle

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Abstract

Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. Methods: The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. Results: The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8-29%) as compared with 56% (28%-154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >. 900. μmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2]. μmol/L) than patients with baseline glutamine ≤. 900. μmol/L (26.6 [18.0]. μmol/L). Glutamine values >. 900. μmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR] = 1.98; p = 0.173). However, glutamine lost predictive significance (OR = 1.47; p = 0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥. 1.0 upper limit of normal (ULN) was highly statistically significant (OR = 4.96; p = 0.013). There was no significant effect of glutamine >. 900. μmol/L on time to first HAC crisis (hazard ratio [HR] = 1.14; p = 0.813), but there was a significant effect of baseline ammonia ≥. 1.0 ULN (HR = 4.62; p = 0.0011). Conclusions: The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels.

Original languageEnglish (US)
Pages (from-to)27-32
Number of pages6
JournalMolecular Genetics and Metabolism
Volume117
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Inborn Urea Cycle Disorder
Glutamine
Urea
Ammonia
Odds Ratio
Hazards
Pediatrics
Biomarkers

Keywords

  • Ammonia
  • Glycerol phenylbutyrate
  • Metabolic disorders
  • RAVICTI

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Lee, B., Diaz, G. A., Rhead, W., Lichter-Konecki, U., Feigenbaum, A., Berry, S. A., ... Scharschmidt, B. F. (2016). Glutamine and hyperammonemic crises in patients with urea cycle disorders. Molecular Genetics and Metabolism, 117(1), 27-32. https://doi.org/10.1016/j.ymgme.2015.11.005

Glutamine and hyperammonemic crises in patients with urea cycle disorders. / Lee, B.; Diaz, G. A.; Rhead, W.; Lichter-Konecki, U.; Feigenbaum, A.; Berry, S. A.; Le Mons, C.; Bartley, J.; Longo, N.; Nagamani, S. C.; Berquist, W.; Gallagher, R. C.; Harding, Cary; McCandless, S. E.; Smith, W.; Schulze, A.; Marino, Miguel; Rowell, R.; Coakley, D. F.; Mokhtarani, M.; Scharschmidt, B. F.

In: Molecular Genetics and Metabolism, Vol. 117, No. 1, 01.01.2016, p. 27-32.

Research output: Contribution to journalArticle

Lee, B, Diaz, GA, Rhead, W, Lichter-Konecki, U, Feigenbaum, A, Berry, SA, Le Mons, C, Bartley, J, Longo, N, Nagamani, SC, Berquist, W, Gallagher, RC, Harding, C, McCandless, SE, Smith, W, Schulze, A, Marino, M, Rowell, R, Coakley, DF, Mokhtarani, M & Scharschmidt, BF 2016, 'Glutamine and hyperammonemic crises in patients with urea cycle disorders', Molecular Genetics and Metabolism, vol. 117, no. 1, pp. 27-32. https://doi.org/10.1016/j.ymgme.2015.11.005
Lee B, Diaz GA, Rhead W, Lichter-Konecki U, Feigenbaum A, Berry SA et al. Glutamine and hyperammonemic crises in patients with urea cycle disorders. Molecular Genetics and Metabolism. 2016 Jan 1;117(1):27-32. https://doi.org/10.1016/j.ymgme.2015.11.005
Lee, B. ; Diaz, G. A. ; Rhead, W. ; Lichter-Konecki, U. ; Feigenbaum, A. ; Berry, S. A. ; Le Mons, C. ; Bartley, J. ; Longo, N. ; Nagamani, S. C. ; Berquist, W. ; Gallagher, R. C. ; Harding, Cary ; McCandless, S. E. ; Smith, W. ; Schulze, A. ; Marino, Miguel ; Rowell, R. ; Coakley, D. F. ; Mokhtarani, M. ; Scharschmidt, B. F. / Glutamine and hyperammonemic crises in patients with urea cycle disorders. In: Molecular Genetics and Metabolism. 2016 ; Vol. 117, No. 1. pp. 27-32.
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AU - Feigenbaum, A.

AU - Berry, S. A.

AU - Le Mons, C.

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