Cytochrome c oxidase deficient muscle fibres: substantial variation in their proportions within skeletal muscles from patients with mitochondrial myopathy

Neuromuscul Disord. 2005 Nov;15(11):768-74. doi: 10.1016/j.nmd.2005.06.018. Epub 2005 Sep 28.


Mitochondrial DNA (mtDNA) disease is a common cause of myopathy and the presence of histochemically demonstrated cytochrome c oxidase (COX) deficiency is an extremely useful diagnostic feature. However, there is currently no quantitative information regarding the variability of COX deficiency within or between muscles. This study addresses this issue by studying a number of skeletal muscle samples obtained at post-mortem from three patients with mitochondrial disease due to established mitochondrial DNA defects. COX deficient muscle fibres were enumerated in sections of these muscles and analysed according to patient, individual muscle, position within a particular muscle and sample size. Descriptive statistics were generated followed by an analysis of variance (ANOVA) to assess the effect of these parameters on the mean percentage of COX deficient fibres. We observed statistically significant variation in the percentage of COX deficient fibres within individual muscles from each patient for samples sizes of between 100 and 400 fibres. Our results have implications for the way in which biopsies of skeletal muscle are used for the assessment of disease severity, progression and response to treatment.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Analysis of Variance
  • Blotting, Southern / methods
  • Cytochrome-c Oxidase Deficiency / complications*
  • Cytochrome-c Oxidase Deficiency / pathology
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism*
  • Female
  • Histocytochemistry / methods
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / enzymology*
  • Mitochondrial Myopathies / etiology*
  • Mitochondrial Myopathies / pathology
  • Muscle, Skeletal / enzymology*
  • Reverse Transcriptase Polymerase Chain Reaction / methods


  • Electron Transport Complex IV