title: Glutamine and hyperammonemic crises in patients with urea cycle disorders.
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.
authors.affiliation: Baylor College of Medicine, Houston, TX, USA. Electronic address: blee@bcm.edu.
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Diaz
authors.affiliation: The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: W
authors.initials: W
authors.lastname: Rhead
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: U
authors.initials: U
authors.lastname: Lichter-Konecki
authors.affiliation: Univ. of CA, San Diego, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Feigenbaum
authors.affiliation: Univ. of Minnesota, Minneapolis, MN, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Berry
authors.affiliation: National Urea Cycle Disorders Foundation, Pasadena, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Le Mons
authors.affiliation: Miller Children's Hospital, Long Beach, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bartley
authors.affiliation: Univ. of UT, Salt Lake City, UT, USA.
authors.forename: N
authors.initials: N
authors.lastname: Longo
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Nagamani
authors.affiliation: Stanford Univ., Palo Alto, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Berquist
authors.affiliation: Univ. of CA, San Francisco, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Gallagher
authors.affiliation: Oregon Health Sciences, Portland, OR, USA.
authors.forename: C O
authors.initials: CO
authors.lastname: Harding
authors.affiliation: Case Western Reserve Univ. Medical Center, Cleveland, OH, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: McCandless
authors.affiliation: Maine Medical Ctr., Portland, ME, USA.
authors.forename: W
authors.initials: W
authors.lastname: Smith
authors.affiliation: The Hospital for Sick Children, Univ. of Toronto, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Oregon Health Sciences, Portland, OR, USA.
authors.forename: M
authors.initials: M
authors.lastname: Marino
authors.affiliation: MED Technical Consulting, Inc., Union City, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Rowell
authors.affiliation: Horizon Therapeutics, Brisbane, CA, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Coakley
authors.affiliation: Horizon Therapeutics, Brisbane, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mokhtarani
authors.affiliation: Horizon Therapeutics, Brisbane, CA, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Scharschmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005215:Fasting; D005260:Female; D005973:Glutamine / Q000097:blood*; D005990:Glycerol / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000097:blood* / Q000209:etiology; D008297:Male; D010654:Phenylbutyrates / Q000627:therapeutic use; D011237:Predictive Value of Tests; D056806:Urea Cycle Disorders, Inborn / Q000097:blood* / Q000188:drug therapy; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010654:Phenylbutyrates; D005973:Glutamine; D000641:Ammonia; D005990:Glycerol; C570223:glycerol phenylbutyrate
keywords: Ammonia; Glycerol phenylbutyrate; Metabolic disorders; RAVICTI