Peripheral neuropathy associated with mitochondrial disease in children

Dev Med Child Neurol. 2012 May;54(5):407-14. doi: 10.1111/j.1469-8749.2012.04271.x. Epub 2012 Mar 21.


Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease.

Publication types

  • Review

MeSH terms

  • Child
  • DNA Mutational Analysis
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase / genetics*
  • Early Diagnosis
  • Genetic Testing
  • Humans
  • Leigh Disease / diagnosis
  • Leigh Disease / genetics
  • Leigh Disease / rehabilitation
  • Membrane Proteins / genetics
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / rehabilitation
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Optic Nerve Diseases / diagnosis
  • Optic Nerve Diseases / genetics
  • Optic Nerve Diseases / rehabilitation
  • Peripheral Nervous System Diseases / diagnosis*
  • Peripheral Nervous System Diseases / genetics
  • Peripheral Nervous System Diseases / rehabilitation
  • Phenotype
  • Secondary Prevention


  • MT-ATP6 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • Surf-1 protein
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • Mitochondrial Proton-Translocating ATPases