Ethylmalonic encephalopathy

Ethylmalonic encephalopathy is a rare, autosomal recessive genetic disorder defined as an inborn error of metabolism. It affects several body systems, including the gastrointestinal system, circulatory system, and particularly the nervous system.cite journal |author=Zafeiriou DI, Augoustide-Savvopoulou P, Haas D, Smet J, Triantafyllou P, Vargiami E, Tamiolaki M, Gombakis N, van Coster R, Seweil AC, Vianey-Saban C, Gregersen N |title=Ethylmalonic encephalopathy: clinical and biochemical observations |journal=Neuropediatrics |volume=38 |issue=2 |pages=78–82 |year=2007 |pmid=17712735 |doi=10.1055/s-2007-984447 ]

ymptoms

Neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. The body's network of blood vessels is also affected. Children with this disorder may experience rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy.

The signs and symptoms of ethylmalonic encephalopathy are apparent at birth or begin in the first few months of life. Problems with the nervous system typically worsen over time, and most affected individuals survive only into early childhood. A few children with a milder, chronic form of this disorder have been reported.

Pathophysiology

Mutations in the "ETHE1" gene cause ethylmalonic encephalopathy. The "ETHE1" gene provides instructions for making an enzyme that plays an important role in energy production. It is active in mitochondria, which are the energy-producing centers within cells. Little is known about the enzyme's exact function, however.

Mutations in the "ETHE1" gene lead to the production of a nonfunctional version of the enzyme or prevent any enzyme from being made. A lack of the ETHE1 enzyme impairs the body's ability to make energy in mitochondria. Additionally, a loss of this 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 remains unclear how a loss of the ETHE1 enzyme leads to progressive brain dysfunction and the other features of ethylmalonic encephalopathy.

This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder.

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