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, C. O. Harding, S. E. McCandless, W. Smith, A. Schulze, M. Marino, R. Rowell, D. F. Coakley, M. MokhtaraniB. F. Scharschmidt

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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
Issue number1
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
The authors gratefully acknowledge the efforts of the staff at the clinical study who made these analyses possible, including N. Schrager (Icahn School of Medicine at Mount Sinai), A. Donovan, J. Crawford, Pediatric TRU Staff, K. Defouw, J. Balliet (The Medical College of Wisconsin), M. Keuth, N. O'Donnell (Long Beach Memorial Hospital), M. Hussain, E. Bailey, A. Orton, M. Ambreen (The Hospital for Sick Children, University of Toronto, ON, Canada), C. Bailey, M.J. Dunkley(The University of Utah), J. Perry, V. de Leon, A. Niemi, K. Cusmano (Stanford University), T. Carlson, J. Parker (University of Minnesota), S. Burr (Children's Hospital Colorado), K. Simpson (Children's National Medical Center), K. Regis (Nationwide Children's Hospital), A. Behrend, T. Marrone (Oregon Health & Sciences University), N. Dorrani (University of California, Los Angeles), C. Heggie (Case Western Reserve University), S. Mortenson (Maine Medical Center), S. Deward (Children's Hospital of Pittsburgh), K. Bart, C. Duggan (SNBL), K. Murray, C. Dedomenico (Tufts Medical Center), C. Gross (University of Florida), L. Brody (Seattle Children's Hospital), M. Mullins, S. Carter, A. Tran, J. Stuff, TCH General Clinical Research Center nursing staff (Baylor), Antonia Martinez, Tristen Moors (Hyperion), as well as the Clinical and Translational Science Awards/General Clinical Research Center Grants ( Baylor College of Medicine , M01RR00188 ; Case Western Reserve University , NIDDK 1K08DK074573 ; Clinical and Translational Science Institute at Children's National Medical Center NIH/NCRR , UL1RR31988 ; Medical College of Wisconsin , UL1RR31973 ; Mount Sinai School of Medicine , UL1RR29887 ; Oregon Health & Science University , UL1RR24140 ; Stanford University , UL1RR25744 ; Tufts University , UL1RR25752 ; University of California, Los Angeles , UL1RR33176 ; University of Colorado , UL1RR25780 ; University of Florida , UL1RR29890 ; University of Minnesota , UL1RR33183 ; University of Pittsburgh , NIH UL1TR000005 ; University of Utah , UL1RR25764 ; University of Washington , UL1TR000423 ). SCS Nagamani is an awardee of the National Urea Cycle Disorders Foundation Research Fellowship and is supported by the Clinical Scientist Development Award by the Doris Duke Charitable Foundation.

Publisher Copyright:
© 2015 The Authors.


  • Ammonia
  • Glycerol phenylbutyrate
  • Metabolic disorders


Dive into the research topics of 'Glutamine and hyperammonemic crises in patients with urea cycle disorders'. Together they form a unique fingerprint.

Cite this