Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation

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In this paper, we describe a distinct clinical subtype of 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria is a group of different metabolic disorders biochemically characterized by increased urinary excretion of 3-methylglutaconic acid. We performed biochemical and genetic investigations, including urine organic acid analysis, NMR spectroscopy, measurement of 3-methylglutaconyl-CoA hydratase activity, cardiolipin levels, OPA3 gene analysis and measurement of the oxidative phosphorylation in four female patients with 3-methylglutaconic aciduria. 3-Methylglutaconic aciduria type I, Barth syndrome, and Costeff syndrome were excluded as the activity of 3-methylglutaconyl-CoA hydratase, the cardiolipin levels, and molecular analysis of the OPA3 gene, respectively, showed no abnormalities. The children presented with characteristic association of hearing loss and the neuro-radiological evidence of Leigh disease. They also had neonatal hypotonia, recurrent lactic acidemia, episodes with hypoglycemia and severe recurrent infections, feeding difficulties, failure to thrive, developmental delay, and progressive spasticity with extrapyramidal symptoms. Our patients were further biochemically characterized by a mitochondrial dysfunction and persistent urinary excretion of 3-methylglutaconic acid.


  • S. Wortmann
  • R. J.T. Rodenburg
  • M. Huizing
  • F. J. Loupatty
  • T. de Koning
  • L. A.J. Kluijtmans
  • U. Engelke
  • R. Wevers
  • J. A.M. Smeitink
  • E. Morava
External organisations
  • Radboud University Medical Center
  • National Human Genome Research Institute
  • Academic Medical Center of University of Amsterdam (AMC)
  • University Medical Center Utrecht
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics


  • 3MGA, Extrapyramidal, Hypoglycemia, Lactic acidemia, Leigh-like syndrome, Mitochondrial, Sensori-neural deafness
Original languageEnglish
Pages (from-to)47-52
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number1
Publication statusPublished - 2006 May 1
Publication categoryResearch
Externally publishedYes