|Classification and external resources|
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 synthesize 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., liver failure).
Acquired vs. congenital
- Acquired hyperammonemia is usually caused by liver diseases, such as viral hepatitis, or excessive alcohol consumption. Cirrhosis of the liver is formed, followed by a shunt of blood directly to the vena cava, resulting in decreased filtration of blood in the liver, which leads to hyperammonemia.
- Congential hyperammonemia is usually due to genetic defects in one of the enzymes of the urea cycle, which leads to lower production of urea from ammonia. The most common genetic defect is ornithine transcarbamylase deficiency, which is X-linked.
The following list includes such examples:
- Online 'Mendelian Inheritance in Man' (OMIM) 311250 - hyperammonemia due to ornithine transcarbamylase deficiency
- Online 'Mendelian Inheritance in Man' (OMIM) 606762 - hyperinsulinism-hyperammonemia syndrome (glutamate dehydrogenase 1)
- Online 'Mendelian Inheritance in Man' (OMIM) 238970 - hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (ornithine translocase)
- Online 'Mendelian Inheritance in Man' (OMIM) 237310 - hyperammonemia due to N-acetylglutamate synthetase deficiency
- Online 'Mendelian Inheritance in Man' (OMIM) 237300 - hyperammonemia due to carbamoyl phosphate synthetase I deficiency (carbamoyl phosphate synthetase I)
- Online 'Mendelian Inheritance in Man' (OMIM) 238750 - hyperlysinuria with hyperammonemia (genetics unknown)
- Methylmalonic acidemia
- Isovaleric acidemia
- Propionic acidemia
- Carnitine palmitoyltransferase II deficiency
- Transient hyperammonemia of the newborn, specifically in the preterm.
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 arginine (argininosuccinase deficiency) sodium phenylbutyrate and sodium benzoate (ornithine transcarbamoylase deficiency) are pharmacologic agents commonly used as adjunctive therapy to treat hyperammonemia in patients with urea cycle enzyme deficiencies. Sodium phenylbutyrate and sodium benzoate can serve as alternatives to urea for the excretion of waste nitrogen. phenylbutyrate, which is the prodrug of 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.
Hyperammonemia is one of the metabolic derangements that contribute to hepatic encephalopathy. In the brain it causes swelling of astrocytes and stimulation of NMDA-receptors. Overstimulation of NMDA-receptors induces excitotoxicity.
- Arginase deficiency
- N-acetylglutamate synthetase deficiency
- Ornithine translocase deficiency
- Orotic aciduria
- eMedicine - Hyperammonemia : Article by Kazi Imran Majeed
- Ammonul (Sodium Phenylacetate and Sodium Benzoate Injection) clinical pharmacology - prescription drugs and medications at RxList
- CHAPTER 298 – Inborn Errors of Metabolism and Continuous Renal Replacement Therapy in: John J. Ratey MD; Claudio Ronco MD (2008). Critical Care Nephrology: Expert Consult - Online and Print. Philadelphia: Saunders. ISBN 1-4160-4252-0. ISBN2: 9781416042525