Multisystemic inheritable disorders that involve skeletal muscle and are caused by dysfunction of mitochondrial oxidative phosphorylation. Clinical presentations are variable and can include muscle weakness, exercise intolerance, headache, hearing loss, heart defects and failure, coordination and balance disorders, dementia, vision loss, seizures, ptosis, growth retardation, developmental delay, and vomiting and other gastrointestinal illness. Disease onset, progression, and prognosis are dependent on each subtype.

The most common subtypes are Kearns-Sayre syndrome (KSS); Leigh syndrome; mitochondrial DNA deletion syndrome (MDS); mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS); mitochondrial neurogastrointestinal encephalomyopathy (MNGIE); myoclonus epilepsy with ragged red fibers (MERRF); neuropathy, ataxia and retinitis pigmentosa (NARP); Pearson syndrome; and progressive external ophthalmoplegia (PEO).