Exercise intolerance resulting from a muscle-restricted mutation in the mitochondrial tRNA(Leu (CUN)) gene

Ann Med. 2001 Oct;33(7):493-6. doi: 10.3109/07853890109002099.


Background: Some patients presenting with isolated lifelong exercise intolerance and ragged-red fibres, harbour skeletal-muscle restricted mutations in their mitochondrial DNA.

Aim: To identify the molecular defect in a patient presenting with lifelong exercise intolerance, ragged-red fibres and deficiencies of complexes III and IV in skeletal muscle.

Methods: The muscle biopsy was studied for activities of the respiratory chain, histochemical stains, and sequencing the tRNA genes of mitochondrial DNA.

Results: The patient had a heteroplasmic mutation in the tRNA(Leu (CUN)) gene of mitochondrial DNA (G12334A). Clinical and morphological data as well as restriction fragment length polymorphism (RFLP) and single-fibre polymerase chain reaction (PCR) analyses strongly indicate that this molecular defect is the primary cause of the myopathy.

Conclusion: Mutations in any mitochondrial gene should be considered in the differential diagnosis of patients with lifelong exercise intolerance, even when the neurological examination is normal.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Base Sequence
  • Biopsy, Needle
  • Diagnosis, Differential
  • Exercise Tolerance / genetics*
  • Fatigue Syndrome, Chronic / diagnosis*
  • Fatigue Syndrome, Chronic / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Mitochondrial Myopathies / diagnosis*
  • Mitochondrial Myopathies / genetics*
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • RNA, Transfer / genetics*


  • RNA, Transfer