Medical Care
Hyperammonemia is a medical emergency because of the neurotoxicity, which is a direct effect of ammonia on the CNS.
Initial management should consist of protein intake cessation with the provision of as many nonprotein calories as is practical via intravenous routes, oral routes, or both (if possible). More specific therapy depends on the etiology of the hyperammonemia. Hemodialysis, intravenous sodium phenylacetate/benzoate (Ammonul), or both may be needed.
Surgical Care
Liver transplantation has been effective in the long-term treatment of the genetic disorders of ammonia metabolism. Inasmuch as each is a monogenic disorder, a successful surgical outcome is effectively curative. However, many factors must be considered prior to undertaking such a procedure. The long-term outcome data are generally fairly encouraging, with one study reporting a survival rate exceeding 75% at 15 years postoperatively. [9]
There is some conflict in the data concerning survival based on age at transplantation (< 2 years vs >2 years), with some studies reporting an inverse success rate with age, while others suggest the opposite. [10] Some data also suggest adverse cerebral effects of the disorder, independent of the age/severity at surgery, although it remains unclear as to what other factors might be implicated. In selected cases of acquired hepatic disease, a portocaval shunt may be appropriate.
Consultations
Geneticist
The role of the biochemical geneticist is to assist in interpretation of available laboratory tests toward a diagnosis of a specific genetic entity. Treatment must be guided by a professional experienced in the treatment of urea cycle disorders. This professional may be a biochemical geneticist, clinical geneticist, endocrinologist, or pediatrician, depending on the expertise available at a specific institution.
If such a diagnosis is confirmed, the patient requires long-term follow-up with a geneticist.
Guidelines for clinical genetic evaluation of children with mental retardation or developmental delays have been established. [11]
Neurologist
The role of the neurologist is to provide a basic status evaluation for later reference during follow-up care.
This evaluation is especially useful in the primary genetic entities, in which recurrence is a virtual certainty and the risk of additional nervous system compromise exists.
Gastroenterologist
A gastroenterologist may be of assistance in evaluation of liver disease or when hepatic transplant is considered as therapy for a urea cycle defect. A study of four children with neonatal urea cycle defects concluded that, given the poor prognosis of urea cycle defects with conservative therapy, liver cell transplantation had considerable beneficial effects. [12]
Diet
Dietary therapy greatly depends on the etiologic diagnosis.
Protein restriction is helpful in most cases, and restriction of specific amino acids may be imperative in treatment of particular entities.
Dietary treatment of urea cycle disorders is highly specialized and usually requires consultation with a registered dietitian who works in a metabolic disease clinic.
-
Urea cycle. Compounds that comprise the urea cycle are numbered sequentially, beginning with carbamyl phosphate. At the first step (1), the first waste nitrogen is incorporated into the cycle; also 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 (4); the reaction is mediated by argininosuccinate (ASA) synthetase. Compound 5 is fumaric acid generated in the reaction that converts ASA to arginine (6), which is mediated by ASA lyase.
