Hyperammonemia associated with inherited disorders of
amino acid and organic
acid metabolism is usually manifested by irritability,
somnolence,
vomiting,
seizures, and
coma. Although the majority of these patients present in the newborn period, they may also present in childhood, adolescence, and adulthood with
failure to thrive, persistent
vomiting, developmental delay, or behavioral changes. Persistent
hyperammonemia, if not treated rapidly, may cause irreversible neuronal damage. After the diagnosis of
hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between
urea cycle defects and other causes of hyperammonemic
encephalopathy. In a patient with a presumed inherited metabolic disorder, the aim of
therapy should be to normalize blood
ammonia levels. Recent experience has provided treatment guidelines that include minimizing endogenous
ammonia production and
protein catabolism, restricting
nitrogen intake, administering substrates of the
urea cycle, administering compounds that facilitate the removal of
ammonia through alternative pathways, and, in severe cases, dialysis
therapy. Initiation of dialysis in the encephalopathic patient with
hyperammonemia is indicated if the
ammonia blood level is greater than three to four times the upper limit of normal.
Hemodialysis is the most effective treatment for rapidly reducing blood
ammonia levels. Continuous
hemofiltration and
peritoneal dialysis are also effective modalities for reducing blood
ammonia levels. An improved understanding of the metabolism of
ammonia and neurological consequences of
hyperammonemia will assist the nephrologist in providing optimal care for this high-risk patient population.