title: Clinical heterogeneity in ethylmalonic encephalopathy.
abstract: Ethylmalonic encephalopathy is a recently described inborn error of metabolism characterized clinically by developmental delay and regression, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. We describe monochorionic twins presenting with hypotonia in infancy and diagnosed with ethylmalonic encephalopathy on the basis of biochemical findings. They are compound heterozygote for missense mutations in ETHE1. Magnetic resonance imaging changes affecting the white matter, corpus callosum, and basal ganglia were seen in both patients. At 10 years of age, they have severe axial hypotonia but never displayed petechiae, orthostatic acrocyanosis, or chronic diarrhea. Their clinical courses differ markedly; one had an episode of coma when she was 3 years old and now has spastic quadraparesis and cannot speak. The other can freely use her upper extremities, her pyramidal syndrome being mostly limited to the lower extremities, and can speak 2 languages. These patients illustrate the clinical heterogeneity of ethylmalonic encephalopathy, even in monochorionic twins.
authors.affiliation: Department of Pediatrics, Université de Sherbrooke, Quebec, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pigeon
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Campeau
authors.forename: Denis
authors.initials: D
authors.lastname: Cyr
authors.forename: Bernard
authors.initials: B
authors.lastname: Lemieux
authors.forename: Joe T R
authors.initials: JT
authors.lastname: Clarke
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D018450:Disease Progression; D004200:Diseases in Twins / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics; D020125:Mutation, Missense; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D014427:Twins
chemical_list: C483228:ETHE1 protein, human; D024101:Mitochondrial Proteins; D029543:Nucleocytoplasmic Transport Proteins