ETHE1

The ETHE1 gene provides instructions for making an enzyme that is involved in energy production. This enzyme is active throughout the body in mitochondria (the energy-producing centers in cells), where it may form part of a larger protein complex. Little is known about the enzyme's function in mitochondria.

ethylmalonic encephalopathy - caused by mutations in the ETHE1 gene

More than 20 different mutations in the ETHE1 gene have been identified in people with ethylmalonic encephalopathy. Most of these mutations lead to the production of an abnormally short, nonfunctional version of the ETHE1 enzyme or prevent cells from making any of this enzyme. These genetic changes impair the body's ability to produce energy in mitochondria. Additionally, a lack of the ETHE1 enzyme allows potentially toxic compounds, including ethylmalonic acid and lactic acid, to build up in the body. Excess amounts of these compounds can be detected in urine.

It is unclear how a loss of the ETHE1 enzyme leads to the progressive features of ethylmalonic encephalopathy. Researchers suggest that a buildup of toxic compounds in the brain could be responsible for the neurologic signs and symptoms. Changes in the blood vessels or in blood flow could also contribute to nervous system damage, leading to the characteristic features of the disorder.