Each cell has several hundred mitochondria in its cytoplasm. Mitochondria contain DNA in a single circular chromosome that codes for 13 proteins, various RNAs, and several regulating enzymes. However, > 90% of mitochondrial proteins are coded by nuclear genes. For practical purposes, all mitochondria are inherited from the cytoplasm of the egg; thus, mitochondrial DNA comes only from the mother.

Mitochondrial disorders (see also Inherited Disorders of Metabolism: Mitochondrial Oxidative Phosphorylation Disorders) can be due to mitochondrial or nuclear DNA abnormalities (eg, deletions, duplications, mutations). High-energy tissues (eg, muscle, heart, brain) are particularly at risk of malfunction due to mitochondrial abnormalities. Particular mitochondrial DNA abnormalities result in characteristic manifestations (see Table 2: General Principles of Medical Genetics: Mitochondrial Disorders). Mitochondrial disorders are equally common among males and females.

Table 2
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Mitochondrial Disorders Disorder Description Chronic progressive external ophthalmoplegia Progressive paralysis of the extraocular muscles usually preceded by bilateral, symmetric, progressive ptosis that begins months to years earlier Kearns-Sayre syndrome A multisystem variant of chronic progressive external ophthalmoplegia that also includes heart block, retinitis pigmentosa, and CNS degeneration Leber's hereditary optic neuropathy Variable but often devastating bilateral visual loss that often occurs in adolescents and that is due to a point mutation in mitochondrial DNA MERRF syndrome Myoclonic epilepsy, ragged red fibers, dementia, ataxia, and myopathy MELAS syndrome Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes Pearson's syndrome Sideroblastic anemia, pancreatic insufficiency, and progressive liver disease that begins in the first few months of life and is frequently fatal in infants

Mitochondrial abnormalities may occur in many common disorders such as some types of Parkinson's disease (which may involve large mitochondrial deletions in the cells of the basal ganglia) and many types of muscle disorders.

Maternal inheritance patterns characterize abnormalities of mitochondrial DNA. Thus, all offspring of an affected female are at risk of inheriting the abnormality, but no offspring of an affected male are at risk. Variability in clinical manifestations is the rule and may be due in part to variable mixtures of inherited mutant and normal mitochondrial genomes within cells and tissues.

Last full review/revision May 2007 by Judith G. Hall, MD