Mitochondrial Myopathies (MM)

Signs and Symptoms

Breathing issues

Sometimes mitochondrial myopathies can cause significant weakness in the muscles that support breathing. Mitochondrial encephalomyopathies (diseases caused by a defect in oxidative phosphorylation, 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 conduction block. Cardiac muscle damage (cardiomyopathy) also may 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), 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.

A severe infant and/or childhood encephalomyopathy phenotype that usually presents at birth with hypotonia, respiratory muscle weakness, and feeding difficulty may have associated brain, heart, liver, or kidney involvement. These infants usually die before reaching one year of age. Also, an infantile presentation with a severe pure myopathy, lacking multisystem involvement, has been described.^1,2

Symptoms of mitochondrial myopathies

The main symptoms of mitochondrial myopathies are muscle weakness and atrophy (shrinking) and exercise intolerance. Furthermore, mitochondrial disorders can occasionally present only with these muscle symptoms and elevated or normal serum creatine kinase (CK), myalgia, or, less often, rhabdomyolysis (toxic muscle breakdown). It is important to remember that these symptoms 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 diseases 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. In addition, psychiatric symptoms can be more difficult to treat in patients with mitochondrial myopathes because many psychotropic medications can negatively impact mitochondrial function.

Exercise intolerance

Exercise intolerance, also called exertional fatigue, 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 can seem to temporarily lock the muscles. Injury-induced pain is caused by a process of acute muscle breakdown called 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 the overexertion or several hours afterward.

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, headaches and seizures often are 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.

References

1. Rubio-Gozalbo, M. E. et al. Clinical differences in patients with mitochondriocytopathies due to nuclear versus mitochondrial DNA mutations. Hum. Mutat. (2000). doi:10.1002/1098-1004(200006)15:6<522::AID-HUMU4>3.0.CO;2-Y
2. Skladal, D. et al. The clinical spectrum of mitochondrial disease in 75 pediatric patients. Clin. Pediatr. (Phila). (2003). doi:10.1177/000992280304200806