Medical Care
Depending on clinical status and the blood ammonia level, the logical first step is to reduce protein intake and to attempt to maintain energy intake. Initiate intravenous infusion of 10% glucose (or higher, if administered through a central line) and lipids.
Intravenous sodium benzoate and sodium phenylacetate may be helpful. Arginine is usually administered with benzoate and phenylacetate. This is best administered in the setting of a major medical center where facilities for hemodialysis in infants is available.
Glycerol phenylbutyrate is a pre-prodrug that undergoes metabolism to form phenylacetate. Results of a phase 3 study comparing ammonia control in adults showed glycerol phenylbutyrate was noninferior to sodium phenylbutyrate. [8] In a separate study involving young children ages 2 months through 5 years, glycerol phenylbutyrate resulted in a more evenly distributed urinary output of PAGN over 24 hours and accounted for fewer symptoms from accumulation of phenylacetate. [9]
In patients with an extremely high blood ammonia level, rapid treatment with hemodialysis is indicated.
Metabolic disease specialists should provide long-term care with very close and frequent follow-up.
Consultations
See the list below:
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Medical geneticist
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Metabolic disease specialist
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Dietitian
Diet
An appropriate diet must meet minimal protein requirements for growth and must include scrupulous monitoring.
These requirements change with age, and caloric needs must also be met in order to appropriately use the requisite protein.
Further Outpatient Care
A biochemical geneticist or metabolic disease specialist should closely observe any patient with a diagnosed urea cycle defect, whether partial or complete. Dosage adjustments of oral sodium phenylbutyrate and arginine are often needed.
A trained nutritionist should scrupulously monitor the diet of a patient with carbamoyl phosphate synthetase (CPS) deficiency.
Periodic intellectual and neurologic evaluations are essential to ensure adequacy of treatment.
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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.
