Hyperammonemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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 non-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 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 (eg hepatic failure).

In all cases Hyperammonemia results from defects of the Urea cycle. 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 synthase I)
• Online Mendelian Inheritance in Man (OMIM) 238750 – hyperlysinuria with hyperammonemia (genetics unknown)

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

• Drug side effects: Glycerol phenylbutyrate

• Citrullinemia
• N-acetylglutamate synthetase deficiency
• Ornithine translocase deficiency

• Organic Acidemia Association

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