Laboratory Studies
Affected newborns may experience fulminant hyperammonemia, which remains undetected unless index of suspicion is high.
No routine laboratory tests provide definitive clues. The BUN level may be low, but this is an unreliable index of high blood ammonia. A respiratory alkalosis may be present. Urine orotic acid levels are within reference ranges.
Plasma alanine and glutamine levels are elevated.
Urine amino acids are nondiagnostic in N- acetylglutamate synthetase (NAGS) deficiency but are important in order to help rule out hyperammonemia-hyperornithinemia-homocitrullinuria (HHH) or lysinuric protein intolerance (LPI) (see Differentials).
Urine organic acids are within reference ranges in NAGS deficiency. Ruling out organic acid disorders, which can present with similar signs and symptoms and hyperammonemia, is important.
Definitive diagnosis rests with DNA sequencing; to date, there is no newborn metabolic screen which can detect the defect.
Imaging Studies
Imaging studies generally are not helpful, with the exception of brain imaging when cerebral edema is suspected. Documenting a finding of cerebral edema is important.
Procedures
DNA sequencing is available in selected laboratories; mutation analysis provides a definitive diagnosis
-
Compounds comprising the urea cycle are numbered sequentially, beginning with carbamyl phosphate (1). At this step, the first waste nitrogen is incorporated into the cycle; at this step, N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamyl phosphate synthetase (CPS). Compound 2 is citrulline, the product of condensation between carbamyl phosphate (1) and ornithine (8); the mediating enzyme is ornithine transcarbamylase. Compound 3 is aspartic acid, which is combined with citrulline to form argininosuccinic acid (ASA) (4); the reaction is mediated by ASA synthetase. Compound 5 is fumaric acid generated in the reaction that converts ASA to arginine (6), which is mediated by ASA lyase.
