title: Increased metabolic muscle fatigue is caused by some but not all mitochondrial mutations.
abstract: BACKGROUND
  Excessive muscle fatigue occurs in patients with a mitochondrial encephalomyopathy (MEM), but it is also a frequent problem in patients with other neuromuscular disorders (ONMD).
  
  
  OBJECTIVE
  To determine whether, and to what extent, metabolic muscle fatigue specifically occurs in patients with an MEM.
  
  
  METHODS
  Metabolic muscle fatigue was assessed in a series of 21 patients with an MEM, including 13 patients with chronic progressive external ophthalmoplegia and 8 patients with various mitochondrial point mutations; 27 patients with ONMD; and 25 healthy controls. Isometric twitch force of the ankle dorsiflexors was measured after supramaximal stimulation of peroneal nerves. Six trains of stimuli (of 1 minute's duration with rates from 0.2 to 5 stimuli per second) were given to each subject.
  
  
  RESULTS
  An abnormal decrement of the twitch amplitude that occurred during a stimulation train was found in patients with MEM and in those with ONMD. The decrement of the twitch amplitude of controls and of patients with ONMD was strongly influenced by their muscle force (P<.001). After subtraction of the influence of the muscle force, specific fatigue was notably higher in patients with chronic progressive external ophthalmoplegia than in patients with ONMD and in controls, and it correlated well with elevations of serum lactate. Specific fatigue was also abnormal in a patient with a mitochondrial G7497A mutation, but normal in patients with an A3243G or a G11778A mutation. The heteroplasmy of mitochondrial DNA in muscle correlated neither with the force measures nor with the serum lactate levels.
  
  
  CONCLUSIONS
  Generally, metabolic muscle fatigue accompanies muscular weakness. Specifically, some but not all mitochondrial mutations cause excessive metabolic muscle fatigue.
authors.affiliation: Department of Neurology, University of Regensburg, Germany. wilhelm.schulte-mattler@klinik.uni-regensburg.de
authors.forename: Wilhelm J
authors.initials: WJ
authors.lastname: Schulte-Mattler
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Marcus
authors.initials: M
authors.lastname: Deschauer
authors.forename: Frank N
authors.initials: FN
authors.lastname: Gellerich
authors.forename: Paul A
authors.initials: PA
authors.lastname: Iaizzo
authors.forename: Stephan
authors.initials: S
authors.lastname: Zierz
mesh_terms: D000200:Action Potentials; D000293:Adolescent; D000328:Adult; D004798:Enzymes / Q000378:metabolism; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism*; D009119:Muscle Contraction; D018763:Muscle Fatigue / Q000235:genetics*; D018482:Muscle, Skeletal / Q000502:physiology; D009154:Mutation; D009468:Neuromuscular Diseases / Q000235:genetics / Q000378:metabolism
chemical_list: D004798:Enzymes; D019344:Lactic Acid