title: Ethylmalonic encephalopathy: further clinical and neuroradiological characterization.
abstract: Ethylmalonic encephalopathy (EE) is a rare metabolic disorder with an autosomal recessive mode of inheritance that is clinically characterized by neuromotor delay, hyperlactic acidemia, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Increased urinary levels of ethylmalonic acid and methylsuccinic acid are the main biochemical features of the disorder. We report on two patients affected by EE who showed different clinical and neuroradiological patterns. Patient 1 presented with a chronic clinical course characterized by very slow neuromotor deterioration, ataxia, and dysarthria. In contrast, patient 2 had an acute neonatal onset with severe neuromotor retardation, severe generalized hypotonia, and intractable seizures. Neuroradiological follow-up of patient 1 detected a diffuse hyperintensity on the T2 images at the basal ganglia which remained stable during a period of four years. Patient 2, in contrast, showed a rapid process of cerebral, and in part, cerebellar atrophy. On the basis of our observations, we reviewed the data published in the literature and tried to delineate the natural history of EE, which appears to be characterized by a wide spectrum of severity in the clinical course. No reports on neuroradiological follow-up of EE patients are available in the literature with which to compare our data. Finally, both patients showed a muscle COX deficiency. The pathogenetic implications of such a biochemical finding will be also discussed.
authors.affiliation: Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Viale M. Bracci--Le scotte, 53100 Siena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grosso
authors.forename: Rosa
authors.initials: R
authors.lastname: Mostardini
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Farnetani
authors.forename: Massimo
authors.initials: M
authors.lastname: Molinelli
authors.forename: Rosario
authors.initials: R
authors.lastname: Berardi
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rizzo
authors.forename: Guido
authors.initials: G
authors.lastname: Morgese
authors.forename: Paolo
authors.initials: P
authors.lastname: Balestri
mesh_terms: D020739:Brain Diseases, Metabolic, Inborn / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008314:Malonates / Q000378:metabolism / Q000652:urine; D009132:Muscles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency; D011859:Radiography; D013386:Succinates / Q000378:metabolism / Q000652:urine
chemical_list: D008314:Malonates; D013386:Succinates; C038080:ethylmalonic acid; D011451:Prostaglandin-Endoperoxide Synthases; C039138:methylsuccinic acid