Mitochondrial diseases

Handb Clin Neurol. 2017:145:147-155. doi: 10.1016/B978-0-12-802395-2.00010-9.


Mitochondrial disorders represent a major challenge in medicine. Most of the mitochondrial proteins are encoded by the nuclear DNA (nDNA), whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction. The disease usually affects multiple organs in varying locations and severity; however, there are some forms which affect a single organ. The diagnosis of mitochondrial disorders is based on clinical examination, biochemical and histopathologic examinations, functional studies, and molecular genetic testing. Neuropathologic alterations of the muscle are variable and can range from striking abnormalities, such as cytochrome oxidase-negative and ragged red fibers, to nonspecific or minimal changes. Neuropathologic alterations in the brain show common features in disorders with different genetic background. These are characterized by various degrees of vacuolation in the white and gray matter, regional neurodegeneration with reactive astrogliosis, loss of oligodendrocytes, presence of macrophages and microgliosis, capillary proliferation, and mineralization of vessel walls. The advent of molecular genetics, the discovery of biomarkers and new sequencing platforms to perform targeted exome and whole-genome sequencing have changed traditional approaches to diagnose mitochondrial diseases.

Keywords: mitochondrial DNA; mitochondrial disease; nuclear DNA; ragged red fiber; spongy vacuolation.

Publication types

  • Review

MeSH terms

  • DNA, Mitochondrial / genetics*
  • Humans
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Mitochondria* / pathology
  • Mitochondrial Diseases* / diagnosis
  • Mitochondrial Diseases* / genetics
  • Mitochondrial Diseases* / pathology
  • Mutation / genetics


  • DNA, Mitochondrial