Brain Advance Access published online on April 5, 2007
Brain, doi:10.1093/brain/awm054
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The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene
1Metabolic Disease Center Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics; Academic Hospital Schwabing, Munich, Germany, 2Department of Pediatrics, Child Neurology Unit, Hacettepe University, Ankara, Turkey, 3epartment of Pediatrics, Pediatric Pathology Unit, Hacettepe University, Ankara, Turkey, 4Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Germany, 5Institute of Neuropathology, Evangelisches Krankenhaus Bielefeld, Germany, 6Department of Pediatrics, Pediatric Nutrition and Metabolism Unit, Hacettepe University, Ankara, Turkey, 7Department of Neurology, Columbia University Medical Center, New York, NY, USA, 8GSF National Research Center, Institute of Human Genetics, TU Munich, Germany and 9Medical Genetic Center, Munich, Germany
Correspondence to:
Rita Horváth, MD, Friedrich-Baur-Institute, Ziemssenstr. 1a, 80336 München, Germany Email: rita.horvath{at}lrz.uni-muenchen.de
Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II + III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients. Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type II (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment.
Key Words: coenzyme Q10 myopathy; ETFDH mutations; riboflavin and CoQ10 supplementation; late-onset glutaric aciduria type II
Abbreviations: TMS, tandem mass spectrometry
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Received November 21, 2006. Revised February 16, 2007. Accepted February 26, 2007.
*These authors contributed equally to this work
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