Ethylmalonic Encephalopathy

Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder that affects multiple body systems including the brain, gastrointestinal tract and blood vessels. It is caused by a defective enzyme that plays a part in production of energy for the body. Symptoms may include developmental delay, psychomotor regression, low muscle tone, abnormal movements of the arms and legs, seizures, skin rash, blue discoloration of the hands and feet and chronic diarrhea. Symptoms can be apparent at birth or appear within the first few months of life. Functions of the nervous system progressively worsen and most affected individuals only survive to early childhood. There is no cure for EE; however medical surveillance and care may help to improve some symptoms and overall condition of life. EE is caused by pathogenic variants in the ETHE1 gene.

EE is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for EE. However, the risk to have a child affected with EE is increased. Testing of reproductive partners is recommended for carriers of EE.

EE is very rare. It has been reported most commonly in Mediterranean and Arab population.

Genetics Home Reference: Ethylmalonic encephalopathy (http://ghr.nlm.nih.gov)

OMIM [Ethylmalonic encephalopathy: 602473] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing