Mitochondrial disorders

Although mitochondrial disorders have been known for more than thirty years, a major breakthrough in their understanding came much later with the discovery of an impressive number of mutations in mitochondrial DNA (mtDNA). Partial deletions, duplications, or maternally inherited point mutations of mtDNA have been associated with well-defined clinical syndromes. Given the complexity of mitochondrial genetics and biochemistry, the clinical manifestations of mitochondrial disorders are extremely heterogeneous. They range from lesions of single tissues or structures, such as the optic nerve in Leber's hereditary optic neuropathy, or the cochlea in maternally-inherited non-syndromic deafness, to more widespread lesions including myopathies, encephalomyopathies, cardiomyopathies, or complex multisystem syndromes. An increasing number of nuclear disease genes have been discovered in association with syndromes caused by oxidative phosphorylation failure. These advances provide both diagnostic tools and new pathogenetic insights in a rapidly expanding area of neurogenetics.