Clinical progression of mitochondrial myopathy is associated with the random accumulation of cytochrome c oxidase negative skeletal muscle fibres

J Neurol Sci. 2003 Jul 15;211(1-2):63-6. doi: 10.1016/s0022-510x(03)00039-x.


We studied the accumulation of cytochrome c oxidase (COX)-negative skeletal muscle fibres in six patients with a myopathy due to a mitochondrial DNA (mtDNA) defect. Each patient was biopsied on two or more occasions over a period of 3-15 years. Progressive proximal weakness was associated with an increase in the proportion of COX-negative fibres. These fibres were arranged randomly, indicating that each fibre became COX negative independently of the status of neighbouring fibres. The clinical progression of mtDNA myopathy is therefore a consequence of a biochemical defect that develops independently within individual muscle fibres. It is likely that this is due to the clonal expansion of mutant mtDNA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cluster Analysis
  • Confidence Intervals
  • Cytochrome-c Oxidase Deficiency / complications
  • Cytochrome-c Oxidase Deficiency / metabolism*
  • DNA Mutational Analysis / methods
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics
  • Disease Progression
  • Electron Transport Complex IV / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / enzymology*
  • Mitochondrial Myopathies / pathology
  • Mitochondrial Myopathies / physiopathology*
  • Muscle Fibers, Skeletal / enzymology*
  • Muscle, Skeletal / enzymology
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics
  • Mutation
  • Random Allocation


  • DNA, Mitochondrial
  • Electron Transport Complex IV