Treatment is very complex and should be coordinated by a metabolic specialist at a center experienced in the care of urea cycle patients. Therapy is based on reducing plasma ammonia concentration, preventing excess ammonia from being formed, and reducing the amount of nitrogen in the diet while supplying enough for growth.
Reduction of plasma ammonia concentration is accomplished by dialysis and several different methods are available.
The nitrogen scavenger drugs sodium phenylacetate and sodium benzoate provide an alternative pathway for removing excess nitrogen. Intravenous and oral forms of these medications are available (Ammonul and Ucephan). Phenylbutyrate (Buphenyl) has a less offensive odor than the other medications but is available as oral therapy only.
Dietary restrictions in individuals with CPSID are aimed at limiting the amount of protein intake. Children with CPSID are placed on a low-protein, high calorie diet, supplemented by essential amino acids. Treatment may also include citrulline or arginine, to maintain a normal rate of protein formation (synthesis).
Prompt treatment is necessary when individuals have extremely high ammonia levels (severe hyperammonemic episode). Prompt treatment can sometimes prevent coma and severe neurological symptoms. However, in some cases, especially those with complete enzyme deficiency, prompt treatment will not prevent recurrent episodes of hyperammonemia and the potential development of serious complications. In many centers liver transplantation is offered as a more permanent solution to severe CPSID.
Consensus treatment guidelines are available online at the NIH sponsored urea cycle disorders consortium website.
Seizures are treated with phenobarbital or carbamazepine. Valproic acid and intravenous steroids should be avoided, as it can increase blood ammonia levels. Prednisone and other similar steroid compounds should also be avoided because they will trigger a protein catabolic state and hyperammonemia. Inhaled steroids are somewhat safer if necessary.
Of note, the chemotherapy drug cyclophosphamide appears to directly inhibit CPSI.
Affected individuals should receive periodic blood tests to determine the levels of ammonia in the blood. Excessive levels of ammonia should be promptly treated.
Genetic counseling is recommended for affected individuals and their families.