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Mitochondrial DNA Abnormalities


David N. Finegold

, MD, University of Pittsburgh

Last review/revision Jul 2021 | Modified Sep 2022
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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 Mitochondrial Oxidative Phosphorylation Disorders Mitochondrial Oxidative Phosphorylation Disorders Impairment of oxidative phosphorylation often, but not always, causes lactic acidosis, particularly affecting the central nervous system, retina, and muscle. See also Approach to the Patient... read more ) can be due to mitochondrial or nuclear DNA abnormalities (eg, deletions, duplications, mutations Mutations and polymorphisms Certain situations represent aberrant inheritance, often because genes or chromosomes are altered. However, some of these alterations, such as mosaicism, are very common; others, such as polymorphisms... read more ). 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: Some Mitochondrial Disorders Some Mitochondrial Disorders Some Mitochondrial Disorders ). Mitochondrial disorders are equally common among males and females.

Pearls & Pitfalls

  • Mitochondrial disorders can be due to mitochondrial or nuclear DNA abnormalities.

Mitochondrial abnormalities may occur in many common disorders such as some types of Parkinson disease Parkinson Disease Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more (which may involve large mitochondrial deletions in the cells of the basal ganglia) and many types of muscle disorders.


Some Mitochondrial Disorders



Progressive paralysis of the extraocular muscles usually preceded by bilateral, symmetric, progressive ptosis that begins months to years earlier

A multisystem variant of chronic progressive external ophthalmoplegia that also includes heart block, retinitis pigmentosa, and central nervous system degeneration

Variable but often devastating bilateral visual loss that often occurs in adolescents and that is due to a point mutation in mitochondrial DNA

Myoclonic epilepsy with ragged red fibers, dementia, ataxia, and myopathy

Mitochondrial encephalomyopathy with lactic acidosis, and strokelike episodes

Pearson syndrome

Sideroblastic anemia, pancreatic insufficiency, and progressive liver disease that begins in the first few months of life and is frequently fatal in infants

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 these abnormalities mimic a broad range of disorders, which often makes diagnosis extremely difficult. Variability may be due in part to variable mixtures of inherited mutant and normal mitochondrial genomes within cells and tissues.

Key Points

  • Mitochondrial disorders have maternal inheritance patterns.

  • Because clinical manifestations can be subtle and variable, diagnosis can be very difficult.

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