title: The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene.
abstract: 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.
authors.affiliation: Metabolic Disease Center Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics; Academic Hospital Schwabing, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Gempel
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Peter
authors.initials: P
authors.lastname: Schneiderat
authors.forename: Benedikt G H
authors.initials: BG
authors.lastname: Schoser
authors.forename: Volkmar H
authors.initials: VH
authors.lastname: Hans
authors.forename: Beatrix
authors.initials: B
authors.lastname: Pálmafy
authors.forename: Gulsev
authors.initials: G
authors.lastname: Kale
authors.forename: Aysegul
authors.initials: A
authors.lastname: Tokatli
authors.forename: Catarina
authors.initials: C
authors.lastname: Quinzii
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D003067:Coenzymes / Q000172:deficiency / Q000627:therapeutic use; D044927:Electron-Transferring Flavoproteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D012256:Riboflavin / Q000627:therapeutic use; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000172:deficiency / Q000627:therapeutic use
chemical_list: D003067:Coenzymes; D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D014451:Ubiquinone; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C024989:coenzyme Q10; D012256:Riboflavin