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.