Primary mitochondrial myopathies in childhood

Neuromuscul Disord. 2021 Oct;31(10):978-987. doi: 10.1016/j.nmd.2021.08.005.


Primary mitochondrial myopathies are genetic metabolic disorders of mitochondrial dysfunction affecting mainly, but not exclusively, skeletal muscle. Although individually rare, they are the most common inherited metabolic disorders in childhood. They can be similar to other childhood muscle diseases such as congenital myopathies, dystrophies, myasthenic syndromes or metabolic myopathies and a muscle biopsy and genetic testing are important in the differential diagnosis. Mitochondrial myopathies can present at any age but typically childhood onset myopathies have more significant muscle involvement and are caused by genes encoded in the nuclear DNA. Mitochondrial myopathy in infants presents with hypotonia, muscle weakness and difficulty feeding. In toddlers and older children delayed motor development, exercise intolerance and premature fatigue are common. A number of nuclear DNA and mitochondrial DNA encoded genes are known to cause isolated myopathy in childhood and they are important in a range of mitochondrial functions such as oxidative phosphorylation, mitochondrial transcription/translation and mitochondrial fusion/fission. A rare cause of isolated myopathy in children, reversible infantile respiratory chain deficiency myopathy, is non-progressive and typically associated with spontaneous full recovery. Promising targeted treatments have been reported for a number or mitochondrial myopathies including riboflavin in ACAD9 and ETFDH-myopathies and deoxynucleoside for TK2-related disease.

Keywords: Differential diagnosis; Mitochondria; Mitochondrial myopathy; Muscle; Next-generation sequencing; Treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Child
  • DNA, Mitochondrial / genetics
  • Humans
  • Metabolism, Inborn Errors / genetics
  • Mitochondria / pathology
  • Mitochondrial Myopathies / genetics*
  • Muscle Weakness / genetics
  • Muscle, Skeletal / pathology


  • DNA, Mitochondrial