Understanding Mitochondrial Myopathy

Our muscles need energy to function. That energy comes from our mitochondria.

Mitochondria are tiny structures inside almost every cell in our bodies. Each person has trillions of them working to convert oxygen and food into a special type of energy called adenosine triphosphate, or ATP. 90% of the energy our muscles need comes from ATP.

Some cells have a single mitochondrion while others contain hundreds of them. Someone who does not have enough healthy mitochondria, in one or several muscle groups, is said to have mitochondrial myopathy, or mitochondrial disease.

Primary Mitochondrial Myopathy, or PMM, is inherited. It is usually diagnosed when changes, known as mutations, are identified in the genes of our DNA responsible for creating ATP.

Secondary Mitochondrial Myopathy, or SMM, causes similar dysfunction in the mitochondria but the mutations occur in genes not involved in energy production. SMM can either be inherited or develop as a result of exposure to environmental toxins.

Symptoms of Mitochondrial Myopathy

The two most common symptoms of mitochondrial myopathy are muscle weakness and exercise intolerance that leads to unusual feelings of exhaustion. Patients often also have symptoms in their organs. In fact, people with mitochondrial diseases often have symptoms affecting three or more organs. This is because organs like the brain, nerves, heart, pancreas, liver, eyes, and kidneys have high energy needs.

Mitochondrial disease symptoms may include impaired hearing and vision, ataxia (challenges with balance, coordination and speech), seizures, learning disabilities, heart defects, diabetes, and poor growth.

Symptoms affect everyone differently and can vary from mild to life-threatening. Younger people tend to have more debilitating conditions. Children with mitochondrial

disease may have difficulty developing certain skills such as sitting, crawling, walking, speaking and learning.

Because most people with a mitochondrial myopathy experience symptoms that affect multiple systems at the same time, common symptoms are grouped together and referred to as syndromes. Some of these symptoms are outlined below:

There are many factors that make diagnosing mitochondrial myopathy difficult. It affects anyone from children to the elderly, impacts each person differently, and many family physicians are not familiar with the disease.

The process leading to a diagnosis can be long. It usually begins with your physician taking a medical history, conducting a thorough physical evaluation, measuring your strength and endurance, and possibly ordering a series of specialized tests outlined below.

Although receiving a diagnosis can often be a long and uncertain process, knowing exactly which mitochondrial disease you have can help you and your loved ones better understand the disease and plan a path forward. It can also help you understand the long-term realities of the disease and help your health care team create a supportive treatment plan. 

Getting a diagnosis may ensure other diseases are not being overlooked, prevent the wrong treatments from being used, and can stop the need for additional or unnecessary diagnostic testing. Receiving a genetic diagnosis can identify certain inherited mitochondrial diseases. If this is the case, your specialist may recommend that family members see a genetic counsellor and undergo genetic testing. A confirmed genetic diagnosis also aids family planning discussions to learn how the inherited disease may affect future children. There are mitochondrial reproductive options, such as pre-implantation genetic diagnosis (PGD) and tests, such as amniocentesis, to determine mitochondrial disease risk. 

Receiving a genetic diagnosis is also helpful, should you ever be interested in enrolling in a clinical trial. Some clinical trial studies may require con!rmation of diagnosis through genetic testing to participate.

Test

CT or CAT Scan

Computed (Axial) Tomography

Using computers and rotating X-ray machines, the CT creates images to provide detailed information about soft tissues, blood vessels, and bones in various parts of the body.

ECG or EKG

Electrocardiogram

This fast and simple test records the electrical signals in your heart. Electrodes connect to the ECG machine through wires placed on certain spots on your chest, arms and legs. Specialists will be looking for signs of arrhythmia or cardiomyopathy.

Echo

Echocardiogram

An echocardiogram is similar to an ECG but looks for irregularities in the structure of your heart using ultrasound. This test is used to look for signs of cardiomyopathy.

Electromyography

This test assesses the health of muscles and nerves. An electrode is inserted through the skin into an affected muscle. The machine records electrical activity of the muscle and can determine whether muscle weakness is caused by the muscle itself or the nerves that control the muscle. This is often done at the same time as a nerve conduction study (see next page).

Genetic Testing

Genetic testing can determine whether someone has a genetic mutation in the nDNA or mtDNA that causes mitochondrial disease using blood, muscle or saliva samples. Note: there is no genetic test that completely rules out a genetic condition.

Laboratory tests

Blood or urine are standard tests used to detect problems with various organs, including the liver and kidney. These tests also look for elevated lactic acid levels, which is common for those living with mitochondrial disease.

MRI

Magnetic Resonance Imaging

MRI machines use a magnetic field and computer-generated radio waves to create detailed 3D images of organs and tissues that can be evaluated by a specialist.

MR Spectroscopy

Magnetic Resonance Spectroscopy

Using the MRI machine, this test measures levels of phosphocreatine and ATP. Muscles of people with mitochondrial disease are often depleted of these molecules.

Muscle Biopsy

This procedure involves removing a small sample of muscle, usually from the thigh. The sample is then treated with a dye. Muscle fibres affected by mitochondrial disease show as a distinct red and have a ragged appearance.

Nerve Conduction Study

This test evaluates the ability and speed of nerve impulses and can be used to rule out conditions other than PMM.

Neurological Test

This test uses tuning forks, flashlights and/or reflex hammers to evaluate motor and sensory skills, hearing, vision, speech, coordination, and balance.

Spinal Tap or Lumbar Puncture

A needle is inserted between two vertebrae to remove a small amount of cerebrospinal fluid (CSF) to measure folinic acid, protein and/or lactic acid levels. CSF surrounds andprotects the brain and spinal cord. Elevated lactic acid or protein levels as well as low folinic acid may indicate mitochondrial disease.

Because mito can affect each person differently, and many family physicians are unfamiliar with the disease, the process leading to a diagnosis can be long and frustrating. This process usually begins with a family physician sending a referral to a specialist. 

Specialists will take a medical history, conduct a thorough physical evaluation, measure your strength and endurance, and possibly order a series of specialized tests. Certain blood tests may be ordered to look at amino acids, acylcarnitines, lactate, or pyruvate levels. Urine tests are often ordered as they can show indicators of reduced mitochondrial function. A genetic test may be ordered to screen for known, rare and unknown genetic mutations and requires either a saliva, blood or muscle tissue sample. A muscle biopsy may be ordered, which involves removing a small piece of muscle tissue. The tissue is treated with a dye that stains the mitochondria, revealing certain mitochondrial enzymes, proteins or muscle cells with excessive mitochondria.



At this time, there is no cure for mitochondrial disease. The goal of current therapies is to relieve symptoms and improve quality of life. Most therapies involve nutritional supplements and exercise programs with a special diet being a possible solution for some. In many cases, those living with the disease may need devices and therapies to help them breathe, eat, move and learn.

Nutritional supplements

Recommended supplements contain natural substances involved in ATP production in our cells and include:

Creatine: Creatine phosphate typically provides a burst of ATP, which is required for strenuous muscle activity.

Carnitine: Carnitine helps improve the efficiency
of ATP production by recruiting molecules into mitochondria to clean up some of the toxic by-products of ATP production. This is sold as L-carnitine.

Coenzyme Q10 (CoQ10 or ubiquinone/ubiquinol) is an antioxidant and component of the process that makes ATP. For those mitochondrial diseases that are caused by CoQ10 deficiency, supplementation may be helpful.

Mito Cocktail: This is a combination of supplements. The components of the cocktail may vary depending on the condition being treated and may include creatine, L-carnitine, alpha-lipoic acid, riboflavin, and CoQ10.

Exercise

Research shows that some patients with mitochondrial myopathy may see lower fatigue, improved health, and better quality of life when they exercise according to a plan designed specifically for them. Moderate endurance exercise can help increase aerobic fitness. Resistance training can increase strength. It is important to note that new programs should be introduced slowly and that overexertion should be avoided.

There are a variety of different health care specialists that someone diagnosed with mito might seek out, or benefit from having on their team. 

Mito is interdisciplinary, meaning multiple body systems are affected. Depending on what organs are impacted by mito, you may need to see more than one specialist to manage the disease effectively; therefore, the need for multiple healthcare specialties may be necessary. 

Specialists involved in managing mito care include, but are not limited to:

  • Neurologists
  • Geneticists
  • Cardiologists
  • Rheumatologists
  • Epileptologists
  • Physiatrists
  • Dietitians
  • Physiotherapists
  • Orthopaedic surgeons
  • Audiologists
  • Endocrinologists
  • Immunologists
  • Ophthalmologists
  • Sleep medicine specialists

Although receiving a diagnosis can often be a long and uncertain process, knowing exactly which mitochondrial disease you have can help you and your loved ones better understand the disease and plan a path forward. It can also help you understand the long-term realities of the disease and help your health care team create a supportive treatment plan. 

Getting a diagnosis may ensure other diseases are not being overlooked, prevent the wrong treatments from being used, and can stop the need for additional or unnecessary diagnostic testing. Receiving a genetic diagnosis can identify certain inherited mitochondrial diseases. If this is the case, your specialist may recommend that family members see a genetic counsellor and undergo genetic testing. A confirmed genetic diagnosis also aids family planning discussions to learn how the inherited disease may affect future children. There are mitochondrial reproductive options, such as pre-implantation genetic diagnosis (PGD) and tests, such as amniocentesis, to determine mitochondrial disease risk. 

Receiving a genetic diagnosis is also helpful, should you ever be interested in enrolling in a clinical trial. Some clinical trial studies may require con!rmation of diagnosis through genetic testing to participate.

Scientists have recently identified many genetic mutations that cause mitochondrial myopathy.
This means that diagnostic tests may better predict who is most at risk so the onset of disease can be prevented and treatments can be designed.

There are exciting possibilities on the horizon, including:

  • treatments that recruit healthy mitochondria or encourage healthy mitochondria to multiply and outnumber damaged or dysfunctional mitochondria
  • repairing or bypassing defective mitochondria
  • stimulating development of new and healthy mitochondria
  • mitochondria replacement therapy (MRT) which could potentially prevent the passing on of mitochondrial mutations from parent to child

Also encouraging news is that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to two drugs to facilitate and expedite the development of investigational treatments that show potential benefits for those with mitochondrial myopathy. We hope these options will soon extend to Canada.

Mitochondria provide our muscles with the energy they need to function.

ATP is the main source of energy for our cells. It is comprised of adenine, a ribose sugar and three phosphate groups linked together by two high-energy bonds.

Amino acids combine in different patterns to create the essential proteins we need to live, grow and reproduce.

Proteins perform specific functions depending on what amino acids are used to construct them and the order in which they are connected.

DNA (deoxyribonucleic acid) is a long molecule that contains genes. Changes in DNA (nDNA) or mitochondrial DNA (mtDNA) can cause Primary Mitochondrial Myopathy (PMM)

Genes contain special instructions for creating specific proteins that each have a unique purpose. Humans have over 22,000 genes. Some genes are linked to energy production.

Gene mutations are changes to genes that may impair instructions for making proteins. This may result in too many or too few proteins being produced, or for them not to work properly.