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

Molecular Genetics and Metabolism
Saskia B WortmannEva Morava

Abstract

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 dysfu...Continue Reading

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Citations

Aug 6, 2013·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Narges MoghimiAnna M Szekely
Nov 19, 2008·Brain : a Journal of Neurology·Saskia B WortmannEva Morava
Jan 11, 2014·Journal of Inherited Metabolic Disease·Betty Su, Robert O Ryan
May 5, 2010·Journal of Inherited Metabolic Disease·Richard J T Rodenburg
Oct 1, 2010·Journal of Inherited Metabolic Disease·Saskia B WortmannEva Morava
Oct 28, 2015·Annals of Neurology·Nicole J LakeDavid R Thorburn
Oct 9, 2015·Neurogenetics·María Elena Rodríguez-GarcíaFrancisco Martínez-Azorín
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May 28, 2013·Molecular Genetics and Metabolism·Frederic TortAntonia Ribes
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Jul 21, 2020·Pediatric Neurology·Josef FinstererCarla A Scorza
Aug 2, 2021·Metabolism: Clinical and Experimental·T-T TrinhD Bakhos

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