The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene.
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.
Gempel
Klaus
K
Metabolic Disease Center Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics; Academic Hospital Schwabing, Munich, Germany.
Topaloglu
Haluk
H
Talim
Beril
B
Schneiderat
Peter
P
Schoser
Benedikt G H
BG
Hans
Volkmar H
VH
Pálmafy
Beatrix
B
Kale
Gulsev
G
Tokatli
Aysegul
A
Quinzii
Catarina
C
Hirano
Michio
M
Naini
Ali
A
DiMauro
Salvatore
S
Prokisch
Holger
H
Lochmüller
Hanns
H
Horvath
Rita
R
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
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