Mitochondrial Myopathies (MM)

Signs and Symptoms

Muscle weakness and atrophy

The main symptoms of mitochondrial myopathies are fatigue, muscle weakness and atrophy (shrinking) and exercise intolerance. These disorders may present solely with muscle-related symptoms, such as myalgia, with serum creatine kinase (CK) levels that can be normal or elevated, and, less commonly, with episodes of rhabdomyolysis (toxic muscle breakdown). It is important to remember that symptoms may vary greatly from one person to the next, even in the same family.

In some individuals, weakness is most prominent in muscles that control movements of the eyes and eyelids. Two common consequences are the gradual paralysis of eye movements, PEO, and ptosis.

These disorders also can cause significant weakness in the muscles that support breathing. Mitochondrial myopathies may present during periods of increased physiologic stress, such as an illness or surgery/anesthesia.

Exercise intolerance

Exercise intolerance, which may manifest as exertional fatigue or post-exertional malaise, refers to unusual feelings of exhaustion brought on by physical exertion. The degree of exercise intolerance varies greatly among individuals. Some people might have trouble only with athletic activities like jogging, while others might experience problems with everyday activities like walking to the mailbox or lifting a milk carton.

Sometimes, exercise intolerance is associated with painful muscle cramps and/or injury-induced pain. The cramps are actually sharp contractions that seem to temporarily lock the muscles. Injury-induced pain is caused by rhabdomyolysis, leading to leakage of myoglobin from the muscles into the urine (myoglobinuria). Cramps or myoglobinuria usually occur when someone with exercise intolerance “overdoes it,” and can happen during overexertion or several hours afterward.

Breathing issues

Mitochondrial myopathies can cause significant weakness in the muscles that support breathing. Mitochondrial encephalomyopathies (diseases affecting the nervous system and skeletal muscle) also may cause brain abnormalities that alter the brain’s control over breathing.

Cardiac care

Sometimes, mitochondrial diseases directly affect the heart. In these cases, the usual cause is an interruption in the rhythmic beating of the heart, called an arrythmia, which may be in the form of a cardiac conduction block. Cardiac muscle damage (cardiomyopathy) may also occur.

Other potential health issues

Some people with mitochondrial disease experience serious kidney problems, gastrointestinal problems, and/or diabetes. Some of these problems are direct effects of mitochondrial defects in the kidneys, digestive system, or pancreas (in diabetes, pancreatic insufficiency), and others are indirect effects of mitochondrial defects in other tissues.

For example, rhabdomyolysis (acute muscle breakdown) can lead to kidney problems by causing a protein called myoglobin to leak from ruptured muscle cells into the urine. This condition, myoglobinuria, stresses the kidneys’ ability to filter waste from the blood and can cause kidney damage.

Special issues in children

Progressive external ophthalmoplegia (PEO) and drooping of the upper eyelids, called ptosis, typically cause only mild visual impairment in adults; they are potentially more harmful in children with mitochondrial myopathies. Because the development of the brain is sensitive to childhood experiences, PEO or ptosis during childhood can sometimes cause permanent damage to the brain’s visual system.

Due to muscle weakness, brain abnormalities, or a combination of both, children with mitochondrial diseases may have developmental delays. For example, they might take an unusually long time to reach motor milestones such as sitting, crawling, and walking. As they get older, they may be unable to get around as easily as other children their age and may have speech problems and/or learning disabilities.

Severe early-onset presentations can occur. One phenotype resembles Leigh syndrome, with infantile encephalopathy, hypotonia, feeding and respiratory difficulties, and progressive involvement of the brain and other organs; prognosis in these cases is often poor. In contrast, some infants present with a predominantly severe myopathy, such as the myopathic form of mitochondrial DNA depletion syndrome, which may occur with or without involvement of other organs.

Symptoms of encephalomyopathies

A mitochondrial encephalomyopathy typically includes some of the above-mentioned symptoms of myopathy (muscle disease) plus one or more neurological symptoms. Again, these symptoms show a great deal of individual variability in both type and severity.

Hearing impairment, migraine-like headaches, and seizures are among the most common symptoms of mitochondrial encephalomyopathy. In at least one syndrome (MELAS), headaches and seizures are often accompanied by stroke-like episodes.

In addition to affecting the musculature of the eye, a mitochondrial encephalomyopathy can affect the eye itself and parts of the brain involved in vision. For instance, vision loss due to optic atrophy (shrinkage of the optic nerve) or retinopathy (degeneration of some of the cells that line the back of the eye) is a common symptom of mitochondrial encephalomyopathy. These effects are more likely to cause serious visual impairment.

Often, mitochondrial encephalomyopathy causes ataxia, or trouble with balance and coordination. People with ataxia are usually prone to falls.

Additional reading

• Ahuja AS. Understanding mitochondrial myopathies: a review. PeerJ. 2018 May 21;6:e4790. doi: 10.7717/peerj.4790. PMID: 29844960; PMCID: PMC5967365.
• Wen H, Deng H, Li B, Chen J, Zhu J, Zhang X, Yoshida S, Zhou Y. Mitochondrial diseases: from molecular mechanisms to therapeutic advances. Signal Transduct Target Ther. 2025 Jan 10;10(1):9. doi: 10.1038/s41392-024-02044-3. PMID: 39788934; PMCID: PMC11724432.

Last reviewed May 2026.