Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the ETHE1 gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.
Ethylmalonic encephalopathy: phenotype-genotype description and review of its management
