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

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

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.

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

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.

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.