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Neuropediatrics 2007; 38(2): 78-82
DOI: 10.1055/s-2007-984447
Original Article

© Georg Thieme Verlag KG Stuttgart · New York

Ethylmalonic Encephalopathy: Clinical and Biochemical Observations

D. I. Zafeiriou 1 , P. Augoustides-Savvopoulou 1 , D. Haas 2 , J. Smet 3 , P. Triantafyllou 1 , E. Vargiami 1 , M. Tamiolaki 4 , N. Gombakis 1 , R. van Coster 3 , A. C. Sewell 5 , C. Vianey-Saban 6 , N. Gregersen 7
  • 1Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 2University Hospital for Pediatric and Adolescent Medicine, Division of Metabolic Diseases, Heidelberg, Germany
  • 3Mitochondrial Investigations Laboratory, University Hospital, Ghent, Belgium
  • 4Pediatric Intensive Care Unit, “Hippokratio” General Hospital, Thessaloniki, Greece
  • 5Metabolic Laboratory, University Children's Hospital, Frankfurt am Main, Germany
  • 6Service de Biochimie Pediatrique, Centre de Reference Maladie Metaboliques, Hopital Debrousse, Lyon, France
  • 7Research Unit for Molecular Medicine, Institute of Clinical Medicine, Hospital and Faculty of Health Sciences, Aarhus University, Aarhus, Denmark
Further Information

Publication History

received 17.5.2006

accepted 30.5.2007

Publication Date:
22 August 2007 (online)

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Abstract

Ethylmalonic encephalopathy (EE) is a rare, recently defined inborn error of metabolism which affects the brain, gastrointestinal system and peripheral blood vessels and is characterized by a unique constellation of clinical and biochemical features. A 7-month-old male, who presented with psychomotor retardation, chronic diarrhea and relapsing petechiae is described with the objective of highlighting the biochemical and neuroradiological features of this disorder as well as the effect of high-dose riboflavin therapy. Urinary organic acid analysis revealed markedly increased excretion of ethylmalonic acid, isobutyrylglycine, 2-methylbutyrylglycine and isovalerylglycine. Acylcarnitine analysis in dried blood spots showed increased butyrylcarnitine. Short-chain acyl-CoA dehydrogenase (SCAD) activity in muscle was normal as were mitochondrial OXPHOS enzyme activities in cultured skin fibroblasts. In skeletal muscle the catalytic activity of complex II was decreased. Brain MRI revealed bilateral and symmetrical atrophy in the fronto-temporal areas, massive enlargement of the subarachnoid spaces and hyperdensities on T2 sequences of the basal ganglia. Mutation analysis of the ETHE1 gene demonstrated homozygosity for the Arg163Gly mutation, confirming the diagnosis of EE at a molecular level. On repeat MRI, a significant deterioration was seen, correlating well with the clinical deterioration of the patient.

Key words

Ethylmalonic encephalopathy - ETHE1 gene - acylcarnitine analysis - MRI - complex II deficiency - muscle

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Correspondence

D. I. ZafeiriouMD, PhD 

1st Department of Pediatrics

Aristotle University of Thessaloniki

Egnatia St. 106

54622 Thessaloniki

Greece

Phone: +30/2310/24 18 45

Fax: +30/2392/06 31 86

Email: jeff@med.auth.gr