Ethylmalonic encephalopathy
| Ethylmalonic encephalopathy | |
|---|---|
 | |
| Ethylmalonic encephalopathy has an autosomal recessive pattern ofinheritance. | |
| Specialty | Medical genetics |
Ethylmalonic encephalopathy(EE) is a rareautosomalrecessiveinborn error of metabolism.Patients affected with EE are typically identified shortly after birth, with symptoms includingdiarrhea,petechiaeandseizures.[1][2]The genetic defect in EE is thought to involve an impairment in the degradation of sulfide intermediates in the body.Hydrogen sulfidethen builds up to toxic levels.[3]EE was initially described in 1994.[4]Most cases of EE have been described in individuals of Mediterranean or Arabic origin.[3]
Signs and symptoms
[edit]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.[3]EE is often identified by urine organic acid analysis, the excretion of ethylmalonic acid, methylsuccinic acid, isobutyrylglycine and isovalerylglucine. Patients will also often have elevatedthiosulphateconcentration in their urine.[5]
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, and there can be considerablephenotypicvariation, even within families.[6]The life expectancy of individuals with EE is less than ten years.[3]
Pathophysiology
[edit]Mutations in theETHE1gene cause ethylmalonic encephalopathy.[7]TheETHE1gene makes an enzyme that plays an important role in energy production. It is active inmitochondria,which are the energy-producing centers within cells. Little is known about its exact function, however.
Mutations in theETHE1gene lead to the production of a defective version of the enzyme or prevents the enzyme from being made. A lack of the ETHE1 enzyme impairs the 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.
Ethylmalonic encephalopathy is an autosomal recessive disorder, which means the defective gene is located on anautosome,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.
Diagnosis
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Treatment
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References
[edit]- ^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 (2007). "Ethylmalonic encephalopathy: clinical and biochemical observations".Neuropediatrics.38(2): 78–82.doi:10.1055/s-2007-984447.PMID17712735.
- ^Tiranti, V.; Viscomi, C.; Hildebrandt, T.; Di Meo, I.; Mineri, R.; Tiveron, C.; Levitt, M.; Prelle, A.; Fagiolari, G.; Rimoldi, M.; Zeviani, M. (2009). "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in ethylmalonic encephalopathy".Nature Medicine.15(2): 200–205.doi:10.1038/nm.1907.PMID19136963.S2CID5970257.
- ^abcd"Encephalopathy, Ethylmalonic".Johns Hopkins University.Retrieved2012-05-12.
- ^Burlina, A. B.; Dionisi-Vici, C.; Bennett, M. J.; Gibson, K. M.; Servidei, S.; Bertini, E.; Hale, D. E.; Schmidt-Sommerfeld, E.; Sabetta, G.; Zacchello, F.; Rinaldo, P. (1994). "A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts".The Journal of Pediatrics.124(1): 79–86.doi:10.1016/S0022-3476(94)70257-8.PMID8283379.
- ^Drousiotou, A.; Dimeo, I.; Mineri, R.; Georgiou, T.; Stylianidou, G.; Tiranti, V. (2011). "Ethylmalonic encephalopathy: Application of improved biochemical and molecular diagnostic approaches".Clinical Genetics.79(4): 385–390.doi:10.1111/j.1399-0004.2010.01457.x.PMID20528888.S2CID42297374.
- ^Pigeon, N.; Campeau, P. M.; Cyr, D.; Lemieux, B.; Clarke, J. T. R. (2009). "Clinical Heterogeneity in Ethylmalonic Encephalopathy".Journal of Child Neurology.24(8): 991–996.doi:10.1177/0883073808331359.PMID19289697.S2CID10613701.
- ^Mineri R, Rimoldi M, Burlina AB, Koskull S, Perletti C, Heese B, Von Döbeln U, Mereghetti P, Di Meo I, Invernizzi F, Zeviani M, Uziel G, Tiranti V (Jul 2008). "Identification of new mutations in the ETHE1 gene in a cohort of 14 patients presenting with ethylmalonic encephalopathy".Journal of Medical Genetics.45(7): 473–8.doi:10.1136/jmg.2008.058271.PMID18593870.S2CID42504096.
External links
[edit]- Ethylmalonic encephalopathyatNLMGenetics Home Reference