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Genetics Home Reference: your guide to understanding genetic conditions
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Ethylmalonic encephalopathy

Reviewed August 2006

What is ethylmalonic encephalopathy?

Ethylmalonic encephalopathy is an inherited disorder that affects several body systems, particularly the nervous system. Neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. The body's network of blood vessels (the vascular system) 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.

How common is ethylmalonic encephalopathy?

About 30 individuals with this condition have been identified worldwide, mostly in Mediterranean and Arab populations. Although ethylmalonic encephalopathy appears to be very rare, researchers suggest that some cases have been misdiagnosed as other neurologic disorders.

What genes are related to ethylmalonic encephalopathy?

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.

Related Gene(s)

Changes in this gene are associated with ethylmalonic encephalopathy.

  • ETHE1

How do people inherit ethylmalonic encephalopathy?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of ethylmalonic encephalopathy?

These resources address the diagnosis or management of ethylmalonic encephalopathy and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/ethylmalonic-encephalopathy)
  • Genetic Testing Registry: Ethylmalonic encephalopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1865349)
  • MedlinePlus Encyclopedia: Skin discoloration - bluish (http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm)

You might also find information on the diagnosis or management of ethylmalonic encephalopathy in Educational resources (http://www.ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/ethylmalonic-encephalopathy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about ethylmalonic encephalopathy?

You may find the following resources about ethylmalonic encephalopathy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for ethylmalonic encephalopathy?

  • EME
  • Encephalopathy, petechiae, and ethylmalonic aciduria
  • EPEMA syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about ethylmalonic encephalopathy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding ethylmalonic encephalopathy?

aciduria ; acrocyanosis ; autosomal ; autosomal recessive ; cell ; chronic ; encephalopathy ; enzyme ; gene ; hypotonia ; inherited ; lactic acid ; mitochondria ; muscle tone ; nervous system ; neurologic ; newborn screening ; oxygen ; petechiae ; recessive ; screening ; syndrome ; toxic ; vascular

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Burlina A, Zacchello F, Dionisi-Vici C, Bertini E, Sabetta G, Bennet MJ, Hale DE, Schmidt-Sommerfeld E, Rinaldo P. New clinical phenotype of branched-chain acyl-CoA oxidation defect. Lancet. 1991 Dec 14;338(8781):1522-3. (http://www.ncbi.nlm.nih.gov/pubmed/1683940?dopt=Abstract)
  • Di Rocco M, Caruso U, Briem E, Rossi A, Allegri AE, Buzzi D, Tiranti V. A case of ethylmalonic encephalopathy with atypical clinical and biochemical presentation. Mol Genet Metab. 2006 Dec;89(4):395-7. Epub 2006 Jul 7. (http://www.ncbi.nlm.nih.gov/pubmed/16828325?dopt=Abstract)
  • García-Silva MT, Ribes A, Campos Y, Garavaglia B, Arenas J. Syndrome of encephalopathy, petechiae, and ethylmalonic aciduria. Pediatr Neurol. 1997 Sep;17(2):165-70. (http://www.ncbi.nlm.nih.gov/pubmed/9367300?dopt=Abstract)
  • Grosso S, Mostardini R, Farnetani MA, Molinelli M, Berardi R, Dionisi-Vici C, Rizzo C, Morgese G, Balestri P. Ethylmalonic encephalopathy: further clinical and neuroradiological characterization. J Neurol. 2002 Oct;249(10):1446-50. (http://www.ncbi.nlm.nih.gov/pubmed/12382164?dopt=Abstract)
  • Heberle LC, Al Tawari AA, Ramadan DG, Ibrahim JK. Ethylmalonic encephalopathy-report of two cases. Brain Dev. 2006 Jun;28(5):329-31. Epub 2006 Jan 10. (http://www.ncbi.nlm.nih.gov/pubmed/16376514?dopt=Abstract)
  • Tiranti V, Briem E, Lamantea E, Mineri R, Papaleo E, De Gioia L, Forlani F, Rinaldo P, Dickson P, Abu-Libdeh B, Cindro-Heberle L, Owaidha M, Jack RM, Christensen E, Burlina A, Zeviani M. ETHE1 mutations are specific to ethylmalonic encephalopathy. J Med Genet. 2006 Apr;43(4):340-6. Epub 2005 Sep 23. (http://www.ncbi.nlm.nih.gov/pubmed/16183799?dopt=Abstract)
  • Tiranti V, D'Adamo P, Briem E, Ferrari G, Mineri R, Lamantea E, Mandel H, Balestri P, Garcia-Silva MT, Vollmer B, Rinaldo P, Hahn SH, Leonard J, Rahman S, Dionisi-Vici C, Garavaglia B, Gasparini P, Zeviani M. Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. Am J Hum Genet. 2004 Feb;74(2):239-52. Epub 2004 Jan 19. (http://www.ncbi.nlm.nih.gov/pubmed/14732903?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2006
Published: December 16, 2014