Distal myopathy with tubular aggregates: a new phenotype associated with multiple deletions in mitochondrial DNA?

• distal myopathy
• multiple mtDNA deletions
• tubular aggregates

Multiple deletions of mitochondrial DNA (mtDNA) are recognised in association with a number of clinical phenotypes, including chronic progressive external ophthalmoplegia (CPEO) and myoneurogastrointestinal encephalopathy (MNGIE). The abnormality may be sporadic or inherited in a recessive or autosomal dominant fashion and is generally considered to be secondary to an abnormality of nuclear DNA.1

Tubular aggregates (TA) are histological bodies consisting of densely packed, double walled tubules 50–70 nm in diameter, originating from the lateral sacs of the sarcoplasmic reticulum.2 Their functional significance remains controversial: in a small group of progressive myopathies, TA form the dominant or even the sole structural abnormality, but more commonly they appear as an accessory histopathological feature in a wide variety of neuromuscular disorders, both inherited and acquired. The strongest association appears to be with periodic paralysis and myotonic disorders, but the finding is by no means consistent, and TA are never more than a minor element of the overall myopathology.2

To the best of our knowledge, an isolated late onset distal myopathy has never been described in association with multiple mtDNA deletions, and high densities of TA have not previously been described in association with mitochondrial myopathy. The present case therefore illustrates two original clinicopathological observations and may be a novel clinical phenotype.

A 73 year old man presented with a history of diffuse muscular pain and progressive gait disturbance over two years. The pain, which preceded the gait disturbance, affected his lower back, buttocks, and upper thighs, was maximal when he was supine, and was not exercise induced. He later noticed that his …