Child Neurology: Ethylmalonic encephalopathy
Periyasamy Govindaraj, Bindu Parayil Sankaran, Madhu Nagappa, Hanumanthapura R. Arvinda, Sekar Deepha, J.N. Jessiena Ponmalar, Sanjib Sinha, Narayanappa Gayathri, Arun B. Taly
Abstract
Ethylmalonic encephalopathy (EE; OMIM #602473) is an autosomal recessive disorder characterized by (1) progressive neurologic impairment, including global developmental delay with periods of regression during illness, progressive pyramidal and extrapyramidal signs, and seizures; and (2) generalized microvascular damage, including petechial purpura and chronic hemorrhagic diarrhea.It leads to premature death.EE is caused by mutations in ethylmalonic encephalopathy protein 1 (ETHE1), and more than 60 different mutations have been reported. 1,2ETHE1 encodes a mitochondrial sulfur dioxygenase involved in the catabolism of hydrogen sulfide (H 2 S). 2 Impairment of sulfur dioxygenase leads to the accumulation of hydrogen sulfide and its derivatives (thiosulphate) in various body fluids and tissues.Higher concentration of H 2 S is toxic and induces direct damage to cell membranes.It inhibits cytochrome c oxidase (COX), increases lactic acid and short-chain acyl-COA dehydrogenase, and leads to elevation of ethyl malonate and C4/C5 acylcarnitine in muscle and brain. 2 We describe the clinical phenotype and MRI, pathologic, and biochemical findings of a patient with EE from India who had a novel homozygous c.493 G>C (p.D165H) variation in ETHE1.