Hyperammonemia therapy

Urea cycle defects Failure to convert ammonia to urea via urea cycle (Fig. 40-5). Coma, convulsions, vomiting, respiratoryfailure in neonate. Often mistaken for sepsis of the newborn. Mental retardation, failure to thrive, lethargy, ataxia and coma in the older child. Associated with hyperammonemia and abnormalities of blood aminogram Low protein diet Acylation therapy (sodium benzoate, sodium phenylacetate) Arginine therapy in selected syndromes Hepatic transplantation... 

VPA is metabolized in the liver and may cause mild, transient elevations in serum transaminases and lactate dehydrogenase. These elevations usually appear early in therapy, are dose-dependent, and resolve spontaneously. Laboratory abnormalities may be noted in 20% to 40% of patients and do not predispose to the development of more serious hepatic injury. VPA can also interfere with the conversion of ammonia to urea and result in hyperammonemia in approximately 20% of patients. This is usually asymptomatic but infrequently may cause lethargy (77, 350). 

There have been attempts to unravel the mechanism of fluorouracil-induced hyperammonemia, lactic acidosis, and encephalopathy, a rare adverse effect associated with high-dose therapy. The cause is not known, although Krebs cycle metabolism is almost certainly involved (415,416). 

Hyperammonemia has occurred during parenteral nutrition as a component of therapy for renal insufficiency (905). The hyperammonemia presented as a change in mental status, developing about 3 weeks after initiation of parenteral nutrition therapy in most cases the episodes are of increasing duration and paroxysmal. In three of the patients, serum amino acid analysis in the acute phase showed reduced concentrations of ornithine and citrulline (the respective substrate and product of condensation with carbamyl phosphate at its entry into the urea cycle). Concentrations of arginine, the precursor to ornithine, were raised. 

Kimura A, Yoshida I, Ono E, Matsuishi T, Yoshino M, Yamashita F, Yamamoto M, Hashimoto T, Shinka T, Kuhara T, et al. Acute encephalopathy with hyperammonemia and dicarboxyhc aciduria during calcium hopantenate therapy a patient report. Brain Dev 1986 8(6) 601-5. 

Although clinical data suggest that critically ill neonates will benefit from aggressive PN within the first 24 hours of life, some clinicians withhold PN therapy for 2 to 3 days after birth because of concerns for development of adverse effects associated with protein intolerance, such as hyperammonemia, azotemia, and metabolic acidosis. 

In some clinical circumstances, patients with hyperammonemia are treated with antibiotics. Suggest a rational basis for this therapy. QUESTION 1 5.Z... 

Sodium benzoate sodium phenylacetate (25 mg/kg p.o. daily) is used as an adjunctive therapy for the prevention of hyperammonemia in patients with urea cycle enzymopathy. 

A. Hyperammonemia, encephalopathy, or hepatotoxicity related to valproic acid therapy. 

First line therapy for hyperammonemia is directed at reducing the production and absorption of gut-derived ammonia. Non-absorbable antibiotics are better than nonabsorbable disaccharides (e.g., lactulose) in reducing the risk of no improvement... 

As hyperammonemia is considered to be the main cause of hepatic encephalopathy, specific therapy for HE is aimed at the reduction of anunonia production and resorption. Protein restriction has been recommended for a long time to reduce ammonia production. But patients with cirrhosis are hypercatabolic. They may require up to 1.5 g/kg protein per day. Therefore protein restriction has been limited to patients with severe hepatic encephalopathy, and a reduction to less than 1 g protein per kg body weight has been discouraged in the past. A recent clinical study even showed no benefits of protein restriction (Cordoba et al., 2004). 30 cirrhotics who were admitted to the hospital with hepatic encephalopathy were randomized to a low-protein diet or normal protein diet. After two weeks of treatment, the groups did not significantly differ with regard to the course of hepatic encephalopathy. 

Supplementation with N-carbamylglutamate (50-100 mg/kg/day) has been suggested to help restore ureagenesis and improve hyperammonemia however, limited information is available that supports chronic use of N-carbamylglutamate [12, 47, 84]. Similarly, chronic therapy with sodium benzoate (150-250 mg/kg/day) has been proposed to help correct chronic hyperammonemia and hyperglycinemia [19] however, there is... 

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