Mitochondrial Myopathy

Mitochondrial myopathy affects the tiny energy factories inside our cells, leading to muscle weakness and fatigue that can impact daily life in profound ways.

Table of contents

• What is Mitochondrial Myopathy?
• What Causes This Disease?
• Signs and Symptoms
• How is it Diagnosed?
• Treatment Options
• Living with Mitochondrial Myopathy

What is Mitochondrial Myopathy?

Mitochondrial myopathy is a type of muscle disease that happens when the mitochondria — tiny structures inside almost all our cells that act like energy factories — don’t work properly.^[1] These energy factories are responsible for converting the food we eat and the oxygen we breathe into a form of energy called ATP (adenosine triphosphate) that our cells can use.^[4]

When mitochondria are damaged or missing necessary parts, they cannot produce enough energy for the body’s needs.^[5] Because muscles and nerves require large amounts of energy to function, they are often the most affected by mitochondrial problems.^[3] The name itself explains the condition: “myo” means muscle, and “pathos” means disease.^[1]

Mitochondrial myopathies can affect three types of muscles in the body: skeletal muscles (the muscles around bones and eyes), cardiac muscles (the heart muscle), and smooth muscles (the muscles lining the intestines, gastrointestinal tract, bladder, and blood vessels).^[2] Some forms may also cause problems with other organs, including the brain. When the disease causes both prominent muscular and neurological problems, it may be called a mitochondrial encephalomyopathy (encephalo refers to the brain).^[1]

• Skeletal muscles
• Cardiac muscles
• Smooth muscles
• Eyes
• Brain
• Nerves

What Causes This Disease?

Mitochondrial myopathies are genetic conditions.^[4] They are caused by inherited changes (mutations) in genes found in either mitochondrial DNA or nuclear DNA.^[6] More than 350 genes have been linked to these conditions.^[6] These genetic mutations lead to defects in normal mitochondrial function, which is responsible for controlling the majority of energy generation in cells.

You can inherit these conditions from your biological parents in different ways.^[4] Some follow an autosomal dominant pattern (meaning you can get the changed gene from one parent), while others follow an autosomal recessive pattern (meaning you need to get a changed gene from both parents). In some cases, the condition can occur randomly without any history in the biological family.

Certain mitochondrial diseases have what’s called mitochondrial inheritance, which occurs when the mitochondria contain their own DNA that is separate from the DNA in the cell’s nucleus.^[4] For many years, inheritance was believed to be maternal (passed only from mother to child), but it is now known that certain nuclear DNA deletions can also cause mitochondrial myopathy.^[5]

Signs and Symptoms

The symptoms of mitochondrial myopathy vary greatly from person to person, even within the same family.^[3] This happens because a person can have a unique mixture of healthy and defective mitochondria distributed throughout the body. Symptoms can be present at birth, but they can also appear at any age.^[4]

The main symptoms affecting muscles include:^[3]

• Muscle fatigue
• Weakness
• Exercise intolerance (unusual feelings of exhaustion brought on by physical activity)

Chronic Progressive External Ophthalmoplegia (CPEO) is the most common feature of mitochondrial myopathy.^[6] This condition affects the muscles that control eye and eyelid movements. People with CPEO may experience drooping eyelids (called ptosis) and difficulty moving their eyes up and down as well as side to side.^[3] Often, people automatically compensate by moving their necks to look in different directions.

Other symptoms may include:^[6]

• Difficulty swallowing (dysphagia)
• Slow or slurred speech (dysarthria)
• Muscle wasting
• Shortness of breath
• Weakness in the arms and legs

Early onset forms of the disease may also show:^[6]

• Diminished muscle tone (hypotonia)
• Failure to thrive
• Breathing difficulty
• Reduced or absent tendon reflexes

When the disease affects other parts of the body beyond muscles, additional symptoms may occur, including:^[1]

• Seizures and spasms
• Developmental delays
• Deafness
• Stroke-like episodes (often before age 40)
• Visual system defects
• Poor balance
• Heart muscle weakness (cardiomyopathy)
• Liver problems
• Kidney issues
• Diabetes
• Digestive problems such as vomiting, feeling full, or chronic diarrhea

The degree of exercise intolerance varies greatly among individuals.^[3] Some people might have trouble only with athletic activities like jogging, while others may experience exhaustion from everyday activities.

How is it Diagnosed?

A diagnosis of mitochondrial myopathy is based on the presence of symptoms and confirmation by specialized tests.^[6] Healthcare providers may perform or recommend several different types of investigations to determine the nature and extent of the disease.

Diagnostic tests may include:^[6]

• Molecular genetic testing to look for gene mutations
• Exercise testing to evaluate muscle function
• Blood tests to measure levels of lactic acid (a by-product of faulty mitochondria) and metabolic enzymes^[5]
• Muscle biopsy — a sample of muscle tissue examined under a microscope
• Electromyography and nerve conduction studies — electrical tests of muscle and nerve activity
• Brain imaging such as computed tomography (CT) scan or magnetic resonance imaging (MRI)

On muscle biopsy, the tissue of patients with these diseases usually demonstrates “ragged red” muscle fibers when stained with a special dye called Gomori trichrome.^[5] This ragged-red appearance is due to a buildup of abnormal mitochondria underneath the cell’s outer layer.

Blood samples can be useful to detect genetic changes or faults.^[15] For some well-known genetic changes, blood is the preferred tissue to investigate. Urine samples can also be helpful for detecting certain mitochondrial DNA changes.

Diagnosing mitochondrial disease can be challenging because the condition often mimics other diseases, which can lead to delays in diagnosis.^[15] An estimated 1 in 5,000 people has a genetic mitochondrial disease, though this number may be underestimated due to misdiagnosis.^[4]

Treatment Options

There is no specific cure for mitochondrial myopathy at this time.^[6] However, treatments can address symptoms and improve quality of life. Treatment focuses on symptomatic management of disease manifestations.^[8]

Common treatment approaches include:^[6]

• Exercise and physical therapy for skeletal muscle problems. Physical therapy may extend the range of movement of muscles and improve dexterity.^[7]
• Proper nutrition and hydration to support the body
• Vitamin and supplement combinations (sometimes called a “cocktail”) to improve muscle function and general health
• Ophthalmological services for eye symptoms. Surgery can help correct drooping eyelids.^[3]
• Speech therapy for speech difficulties

Multiple vitamins and cofactors are often used, although these therapies are not yet standardized or definitively proven to be effective.^[12] The dietary supplements are used to increase respiratory chain function (such as coenzyme Q10 and riboflavin), serve as antioxidants (such as coenzyme Q10, idebenone, alpha-lipoic acid, vitamins C and E), or function as mitochondrial substrates (such as L-carnitine).

For specific symptoms and complications:^[9]

• Balance and mobility issues can be managed through physical and occupational therapy, and the use of supportive aids such as railings, walkers, canes, braces, or wheelchairs
• Breathing problems may require respiratory support, ranging from occasional pressurized air to permanent ventilator support
• Heart problems often have highly effective treatments including medications, dietary modifications, and lifestyle changes

For a specific form caused by mutations in a gene called TK2, nucleoside therapy might be beneficial, and specific clinical trials might be available.^[6] Genetic counseling for the family is also recommended since the disease is inherited and the pattern of inheritance varies depending on the causative gene.

Living with Mitochondrial Myopathy

The outlook for patients with mitochondrial myopathies varies greatly, depending largely on the type of disease and the degree of involvement of various organs.^[7] In general, more severe forms of the disease appear earlier in life.^[6] The diseases cause progressive weakness and can lead to serious complications.

People affected by mitochondrial diseases can do a great deal to take care of themselves by monitoring their health and scheduling regular medical exams.^[9] Managing energy levels is an important part of living with the condition. Everything the body does — from staying warm to moving and thinking — needs energy, and when mitochondria aren’t working properly, there is less energy available.^[15]

Some helpful considerations:

• There is no reason to avoid alcohol, but moderation is advisable. Excess alcohol can damage muscles and the nervous system.^[15]
• Watch for signs of complications and have symptoms checked regularly by specialists
• Work with a multidisciplinary care team that can address different aspects of the disease
• Connect with patient advocacy and support groups for reliable information and emotional support^[16]

Patient registries and support networks play an important role in advancing research and connecting families affected by mitochondrial disease. These resources provide access to up-to-date information, educational materials, and connections with others who share similar experiences.^[6]