Background: Mitochondrial DNA (mtDNA) mutations are increasingly being recognized as causes of late-onset disease. We report a patient with a late-onset mitochondrial encephalomyopathy caused by a novel G > C transition in mtDNA at position 5556 in the gene encoding the tRNA for tryptophan (MTTW).
Aims: To investigate the cause of disease and assess the pathogenicity of this new mutation.
Methods: Clinical, histopathological and gene sequencing studies. Quantification of the mutation was performed in different tissues from the patient and two relatives and in single muscle fibres.
Results: The mutation was heteroplasmic, segregated in biochemically affected muscle fibres and was absent in blood. The level of mutation in skeletal muscle was higher than in brain, although the brain was clinically the most affected tissue.
Discussion: The 5556G > C mutation appears sporadic. It was not found in any of the family members tested, although some of them manifested disorders that can be associated with mtDNA disease. In addition to reporting the eighth mutation in MTTW, our case illustrates the challenges posed when assigning pathogenicity to mtDNA mutations.