title: Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: George A
authors.identifier: 0000000156889062
authors.initials: GA
authors.lastname: Diaz
authors.affiliation: The Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: William
authors.initials: W
authors.lastname: Rhead
authors.affiliation: Children's National Medical Center, Washington, DC, USA.
authors.forename: Uta
authors.initials: U
authors.lastname: Lichter-Konecki
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Annette
authors.identifier: 0000000279181670
authors.initials: A
authors.lastname: Feigenbaum
authors.affiliation: University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Susan A
authors.identifier: 000000017970688X
authors.initials: SA
authors.lastname: Berry
authors.affiliation: National Urea Cycle Disorders Foundation, Pasadena, California, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Le Mons
authors.affiliation: Miller Children's Hospital, Long Beach, California, USA.
authors.forename: James A
authors.identifier: 0000000274573747
authors.initials: JA
authors.lastname: Bartley
authors.affiliation: University of Utah, Salt Lake City, Utah, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Longo
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sandesh C
authors.initials: SC
authors.lastname: Nagamani
authors.affiliation: Stanford University, Palo Alto, California, USA.
authors.forename: William
authors.identifier: 0000000268273094
authors.initials: W
authors.lastname: Berquist
authors.affiliation: Children's Hospital Colorado, Aurora, Colorado, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Gallagher
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio, USA.
authors.forename: Dennis
authors.identifier: 0000000239711948
authors.initials: D
authors.lastname: Bartholomew
authors.affiliation: Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Cary O
authors.initials: CO
authors.lastname: Harding
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Korson
authors.affiliation: University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: McCandless
authors.affiliation: Maine Medical Center, Portland, Maine, USA.
authors.forename: Wendy
authors.identifier: 0000000321822823
authors.initials: W
authors.lastname: Smith
authors.affiliation: University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Cederbaum
authors.affiliation: University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Derek
authors.identifier: 0000000277622276
authors.initials: D
authors.lastname: Wong
authors.affiliation: University of Washington, Seattle, Washington, USA.
authors.forename: J Lawrence
authors.initials: JL
authors.lastname: Merritt
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Vockley
authors.affiliation: Westchester Medical Center, Westchester, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kronn
authors.affiliation: University of Florida, Gainesville, Florida, USA.
authors.forename: Roberto
authors.identifier: 000000020954451X
authors.initials: R
authors.lastname: Zori
authors.affiliation: Children's National Medical Center, Washington, DC, USA.
authors.forename: Marshall
authors.identifier: 0000000189200110
authors.initials: M
authors.lastname: Summar
authors.affiliation: Accudata Solutions, Lafayette, California, USA.
authors.forename: Douglas A
authors.identifier: 0000000236452776
authors.initials: DA
authors.lastname: Milikien
authors.affiliation: Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marino
authors.affiliation: Hyperion Therapeutics, Brisbane, California, USA.
authors.forename: Dion F
authors.identifier: 0000000232505447
authors.initials: DF
authors.lastname: Coakley
authors.affiliation: Hyperion Therapeutics, Brisbane, California, USA.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mokhtarani
authors.affiliation: Hyperion Therapeutics, Brisbane, California, USA.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Scharschmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005973:Glutamine / Q000097:blood*; D006801:Humans; D022124:Hyperammonemia / Q000097:blood*; D007223:Infant; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D056806:Urea Cycle Disorders, Inborn / Q000097:blood*; D055815:Young Adult
chemical_list: D005973:Glutamine; D000641:Ammonia