Hyperammonemia

Hyperammonemia (or hyperammonaemia) is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary.

Ammonia is a substance that contains nitrogen. It is a product of the catabolism of protein. It is converted to the less toxic substance urea prior to excretion in urine by the kidneys. The metabolic pathways that synthesise urea are located first in the mitochondria and then into the cytosol. The process is known as the urea cycle, which comprises several enzymes acting in sequence.

Primary vs. secondary

 * Primary hyperammonemia is caused by several inborn errors of metabolism that are characterised by reduced activity of any of the enzymes in the urea cycle.
 * Secondary hyperammonemia is caused by inborn errors of intermediary metabolism characterised by reduced activity in enzymes that are not part of the urea cycle (e.g. .Propionic acidemia, Methylmalonic acidemia) or dysfunction of cells that make major contributions to metabolism (e.g. hepatic failure).

Specific types
The following list includes such examples:


 * - hyperammonemia due to ornithine transcarbamylase deficiency
 * - hyperinsulinism-hyperammonemia syndrome (glutamate dehydrogenase 1)
 * - hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (ornithine translocase)
 * - hyperammonemia due to N-acetylglutamate synthetase deficiency
 * - hyperammonemia due to carbamoyl phosphate synthetase I deficiency (carbamoyl phosphate synthetase I)
 * - hyperlysinuria with hyperammonemia (genetics unknown)
 * Methylmalonic acidemia
 * Isovalemic acidemia
 * Propionic acidemia
 * Carnitine palmitoyltransferase II deficiency

Treatment
Treatment centers on limiting intake of ammonia and increasing its excretion. Dietary protein (a source of ammonium) is restricted and caloric intake is provided by glucose and fat. Intravenous sodium phenylacetate and sodium benzoate are pharmacologic agents commonly used as adjunctive therapy to treat hyperammonemia in patients with urea cycle enzyme deficiencies. Sodium phenylacetate and sodium benzoate can serve as alternatives to urea for the excretion of waste nitrogen. Phenylacetate conjugates with glutamine to form phenylacetylglutamine, which is excreted by the kidneys. Similarly, sodium benzoate reduces ammonia content in the blood by conjugating with glycine to form hippuric acid, which is rapidly excreted by the kidneys. A preparation containing sodium phenylacetate and sodium benzoate is available under the trade name Ammonul. Acidification of the intestinal lumen using lactulose can decrease ammonia levels by protonating ammonia and trapping it in the stool. This is a treatment for hepatic encephalopathy.

Sequelae
Hyperammonemia is one of the metabolic derangements that contribute to hepatic encephalopathy.