4.7 Mitochondrial Disorders

Symptoms of mitochondrial disorders vary because a person can have a unique mixture of healthy and defective mitochondria, with a unique distribution of each within the body.

Mitochondrial disorders that mainly cause muscular problems are called mitochondrial myopathies (“myo” means muscle and “pathos “means disease), while mitochondrial disorders that cause both muscular and neurological problems are called mitochondrial encephalomyopathies (encephalo refers to the brain).

Mitochondrial myopathy

The main symptoms of mitochondrial myopathy are:

• Muscle fatigue
• Weakness
• Exercise intolerance

The severity of any of these symptoms varies greatly from one person to the next, even within the same family.

In some individuals, the weakness is most prominent in the muscles that control eye and eyelid movements. This can lead to these muscles eventually becoming paralyzed, called progressive external ophthalmoplegia (PEO). People with PEO may also experience a drooping of the upper eyelids, called ptosis. They also have difficulty moving their eyes up and down and side to side. Often, people automatically compensate for PEO by moving using their necks to look in different directions and might not notice any visual problems. Ptosis can impair vision and cause a listless expression. Surgery can help correct this.

Mitochondrial myopathies can cause weakness and wasting in other muscles of the face and neck, which can lead to difficulty with swallowing and, more rarely, slurred speech. People with mitochondrial myopathies also may experience muscle weakness in their arms and legs.

Exercise intolerance, also called exertional fatigue, refers to unusual feelings of exhaustion brought on by physical exertion. The degree of exercise intolerance varies significantly among individuals. Some people might need help with athletic activities like jogging, while others might experience problems with everyday activities such as walking to the mailbox or lifting a milk carton. In rare instances, this exercise intolerance can lead to muscle breakdown after exercise. This breakdown causes a protein called myoglobin to leak from a person’s muscles into their urine. The leakage, sometimes accompanied by muscle cramps, usually occurs when a person with exercise intolerance “overdoes it” and can happen during physical activity or several hours afterward.

While people with mitochondrial myopathy should avoid overdoing it, moderate exercise can help them maintain strength.

Mitochondrial encephalomyopathy

Mitochondrial encephalomyopathy often includes some symptoms of myopathy plus one or more neurological symptoms.

In addition to affecting the muscles around the eye, mitochondrial encephalomyopathy can affect the eye and parts of the brain involved in vision. For instance, vision loss is a common symptom of mitochondrial encephalomyopathy. This can be caused by shrinkage of the optic nerve or a breakdown of the cells that line the back of the eye.

Other common symptoms of mitochondrial encephalomyopathy include migraine headaches and seizures. There are many effective medications for treating and helping to prevent migraines and seizures, including anticonvulsants and other drugs developed to treat epilepsy.

Hearing loss is another common symptom of mitochondrial disorders. It is caused by damage to the inner ear or the auditory nerve, which connects the inner ear to the brain. This kind of hearing loss is permanent, but it can be managed.  Alternative forms of communication (like sign language), hearing aids, or cochlear implants can help.

Mitochondrial disorders can cause ataxia, which is trouble with balance and coordination. People with ataxia are prone to falls and may need to use supportive aids such as railings, a walker, or a wheelchair. Physical and occupational therapy also may help.

In some cases, mitochondrial disorders can lead to issues with breathing, heart health, kidney issues, diabetes, or digestive problems. People with mitochondrial disorders should get regular health check-ups to identify and monitor these potential problems.

Mitochondrial disorders in children

Although PEO and ptosis typically cause only mild visual impairment in adults, they can be much more harmful in children. During childhood, these conditions can cause permanent damage to the brain’s visual system. Children with signs of PEO or ptosis need to have their vision checked by a specialist.

Children with mitochondrial disorders may have difficulty developing specific skills due to either muscle weakness, neurological problems, or both. For example, they might take longer than usual to learn to sit, crawl, or walk. As they get older, they may be unable to get around as easily as other children their age or may have problems with speech or learning. Children affected by these problems may benefit from early intervention and services such as physical and speech therapy or an individualized education program at school.

To read about different types of mitochondrial disorders, visit this NIH web resource or this mitochondrial myopathies fact sheet from the Muscular Dystrophy Association.

How are mitochondrial disorders diagnosed and treated?

Diagnosing mitochondrial disorders

A diagnosis generally includes:

• An evaluation of medical and family history.
• Physical and neurological exams. The physical exam typically includes tests of strength and endurance, such as an exercise test (which can involve repeatedly making a fist). The neurological exam can consist of tests of reflexes, vision, speech, and basic cognitive (thinking) skills.
• Laboratory tests to look for diabetes, liver and kidney problems, and elevated lactic acid in the blood and urine.  Lactic acid in the cerebral spinal fluid may be measured using a spinal tap or estimated via less invasive MRI imaging.
• EKG (electrocardiogram) to check the heart for signs of arrhythmia and cardiomyopathy.
• Diagnostic imaging, such as CT (computed tomography) or MRI, to inspect the brain for developmental abnormalities or signs of damage. In an individual with seizures, the doctor might order an EEG (electroencephalogram), which involves placing electrodes on the scalp to record brain activity.
• Genetic testing can determine whether someone has a genetic mutation.  Although a positive test result can confirm the diagnosis of a mitochondrial disorder, a negative test result can be more complex to interpret and does not definitively rule out the presence of a genetic mutation. It could mean a person has a mutation that the test could not detect.
• Muscle biopsy involves removing and examining a small sample of muscle tissue. When treated with a dye that stains mitochondria red, muscles affected by mitochondrial disorders often show ragged red fibres—muscle cells (fibres) with excessive mitochondria. Other stains can detect the absence of essential mitochondrial enzymes in the muscle. It also is possible to extract mitochondrial proteins from the muscle and measure their activity. Genetic testing for mutations in mitochondrial DNA is more sensitive than testing for mutations in blood in certain mitochondrial disorders. Noninvasive techniques like MR spectroscopy can examine muscle without taking a tissue sample.

Treating mitochondrial disorders

There are currently no cures or specific treatments for mitochondrial disorders. Generally, treatment is focused on managing symptoms and may include physical and occupational therapy, moderate, physician-led exercise programs, anti-seizure medications, heart medications, vitamins and supplements, or special diets. People with eye and vision symptoms may benefit from assistive devices and surgery, as can individuals with hearing loss. People with any unique issues mentioned below should be monitored by their healthcare provider to track their symptoms and identify appropriate treatments.

People with mild respiratory problems might require occasional respiratory support, such as pressurized air. Someone with more severe problems might require permanent support from a ventilator.

Some mitochondrial disorders may cause cardiomyopathy (heart muscle weakness) or arrhythmia (irregular heartbeat).  Although dangerous, cardiac arrhythmia is treatable with a pacemaker, which stimulates a normal heartbeat.

People with mitochondrial disease may experience gastrointestinal problems, diabetes, and kidney problems. These associated conditions and disorders should be managed with appropriate treatments for each. While some of these problems are directly related to mitochondrial disorders, others may be indirectly affected by the disorder. For example, having myoglobin in a person’s urine causes the kidneys to work harder to filter it out, which can lead to kidney damage.