Medical Care
Immediate cessation of protein intake is mandatory in the face of high blood ammonia levels with provision of supplementary nonprotein energy to close the caloric gap. In most cases of severe hyperammonemia, the patient is given nothing enterally until the hyperammonemia is well controlled.
Treatment of severe hyperammonemia is a true emergency. Reduction of blood ammonia can usually be achieved with intravenous sodium benzoate and phenylacetate. Intravenous sodium benzoate and phenylacetate (Ammonul) [6] was approved in the United States in February, 2005. Alternatively, hemodialysis is usually effective in bringing down the ammonia level, especially with the initial presentation. Exchange transfusion is ineffective and is not generally recommended. Intravenous fluids with glucose and sometimes arginine hydrochloride (HCl) added may be indicated. [7] Maintaining as high of an energy intake as possible is important.
Specific therapy of N- acetylglutamate synthetase (NAGS) deficiency following diagnosis depends on dietary protein restriction and provision of arginine to enhance availability of ornithine and administration of carbamylglutamate (which is not widely available), a functional analogue of NAG. Some patients have done well using this regimen. Whether or not oral sodium phenylbutyrate is helpful in this condition is unclear.
Consultations
NAGS deficiency is an extremely rare disorder with complex treatment.
Consultation with a metabolic disease/medical genetic specialist is usually necessary for assistance with laboratory diagnosis and clinical care. Contact these consultants by telephone if they are not locally available.
Diet
A low-protein diet is generally recommended with dietary supervision under the direction of a dietitian experienced in the care of patients with metabolic disease.
Further Outpatient Care
The patient should be under the care of a biochemical geneticist (metabolic disease specialist) who is an expert in the care of patients with urea cycle defects.
Make medication adjustments based on continued growth and frequently measured plasma amino acids; include the input of a highly trained nutritionist.
Transfer
Consider transferring the patient to a facility equipped for emergent hemodialysis (if the patient is a neonate) and where the appropriate consultants (see Consultations) are immediately available.
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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.
