Understanding Mito

The journey to diagnosis can be a long and often worrisome process. When a diagnosis is finally made, it can bring on feelings of fear and concern. A diagnosis can also provide relief in now knowing the reason behind unexplained symptoms. 

Mitochondrial disease affects each person differently, so ensuring you have access to a supportive healthcare team and reliable information about symptoms, treatment, and their impact means you can navigate the path ahead from an informed position. 

MitoCanada has created this resource, guided by the Mitochondrial Care Network’s 2019 Newly Diagnosed publication, to provide you with credible information and resources you can trust. It is a tool to help you navigate your diagnosis or a future diagnosis and support you in your conversations with your healthcare team, family, friends and colleagues. 

What is mitochondrial disease? Mitochondrial disease (mito) refers to a group of disorders that result when mitochondria cannot produce enough energy or an individual doesn’t have enough healthy mitochondria in their bodies. 

Mitochondria are present in almost every cell in the human body. Creating more than 90% of our required energy, our mitochondria transform the food we eat and the oxygen we breathe into essential energy called ATP (adenosine triphosphate). This energy keeps our hearts beating, lungs breathing, brains thinking, and bodies moving; we simply cannot survive without our mitochondria. 

When mitochondria don’t function properly, they don’t produce the energy we need. Mitochondrial disease commonly affects energy-intensive systems such as the heart, liver, kidneys, brain, muscles, digestive tract, eyes and ears. 

Mitochondrial disease is a broad term that covers a wide range of mitochondrial disorders and syndromes. Mitochondrial disease is divided into two distinct categories – primary mitochondrial disease and secondary mitochondrial dysfunction. The distinction is important as each has a unique genetic basis, diagnosis and treatment strategies. 

Primary mitochondrial disease (PMD): PMDs are long-term, progressive and caused by genetic mutations often inherited from one or both parents. In some rare cases, spontaneous or random mutations occur. This happens at the time of conception or just before conception. PMDs exist from birth, but symptoms can present at any age. 

PMDs are usually diagnosed when mutations are identi!ed in the genes responsible for creating ATP. PMDs can affect almost any part of the body, including the brain, kidneys, liver, nerves, muscles, heart, eyes and ears and can cause physical, developmental, and cognitive disabilities. 

Secondary mitochondrial dysfunction (SMD): Occurs when the mitochondria do not function as well as they should. This dysfunction can be caused by gene mutations that are either inherited or develop at some point during a person’s life. They can be caused by environmental factors such as exposure to a drug, toxic substance, or viral infection. These types of gene mutations do not directly affect how energy is generated but impact the function of mitochondria in some way. 

Environmental exposure to cigarette smoke, asbestos and drug toxicity can also impair the mitochondria’s ability to produce energy, creating dysfunction (1). SMD can also be acquired through illness, infection, inflammation, aging and strenuous medical procedures. 

Other terms used for mitochondrial disease: Mitochondrial cytopathy and mitochondrial myopathy are other terms used in place of mitochondrial disease. These older terms are used less often. The medical community is trying to use more straightforward terms, like primary mitochondrial disease, to eliminate patient and caregiver confusion or misconceptions. 

Historically, the term “possible mitochondrial disease” has been used when mito is suspected but cannot be confirmed with a genetic diagnosis. The challenge in using “possible mitochondrial disease” is that there are many conditions that look like or are similar to mito but are not mito. When genetic testing cannot con!rm a mitochondrial disease, using the term “possible mitochondrial disease” can cause harm by creating anxiety or delay finding an accurate diagnosis. Not having an accurate diagnosis may result in providing the wrong care and management to a patient. 

Currently, “diagnosis uncertain” with a detailed description of symptoms and test results is the preferred term when mito cannot be genetically con!rmed. 

Mito symptoms can be mild or severe, differ by individual, and depend on which cells of the body are affected. The two most common mito symptoms are muscle weakness and exercise intolerance which leads to feelings of exhaustion. 

What causes mitochondrial disease? In many patients, mitochondrial disease is caused by an inherited gene mutation or multiple mutations. In others, external environmental factors may be responsible for mitochondrial dysfunction. Many different types of mito can develop in patients in contrasting ways. It often takes more work for healthcare teams to define direct causes. 

Primary mitochondrial disease (PMD) exists from birth and is genetic, meaning the disease is inherited or passed down from one or both parents. In some rare cases, mito can be caused by a “spontaneous mutation”, meaning it occurs randomly at or before conception (2). 

Within the mitochondria are two types of genetic material, mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). mtDNA is passed on from the mother to her children, and nDNA is passed on from both parents (3). 

Maternal inheritance: A mother with a mitochondrial DNA (mtDNA) gene mutation can pass along the mutation to all of her children. Typically, all children will be affected but with varying degrees of severity, from no symptoms to severe disease. This does not mean that all of her children will be affected in the same way, and it is rarely possible to predict how children will be a”ected (causing stress for family planning) (4). 

Autosomal recessive inheritance: The nuclear DNA (nDNA) that makes up part of the mitochondria is inherited by both parents, half from each. Autosomal recessive mitochondrial disease can only be passed on if BOTH parents are carriers. Meaning, each parent carries the mutated gene but not the disease, so they do not have any symptoms (5). 

When both parents are carriers, there is a 25% chance of having a child that will not carry the mutation nor the disease, a 25% chance of having a child with mito and a 50% chance of having a child who will carry the mutation but will not have mito (6). 

Autosomal dominant inheritance: If one parent has a dominant nDNA gene mutation and the other parent does not have any nDNA mutations, 50% of their children will inherit the mutation with the disease and symptoms, and 50% of their children will inherit normal genes; therefore, no disease or symptoms (7). 

X-linked inheritance: X-linked conditions are caused by genetic variants on the X chromosome, one of the two sex chromosomes. Because females have two X chromosomes and males only one, the disorders can appear different in the two sexes. Males are nearly always more severely affected. The rules for inheritance are also different since men cannot transmit X-linked genes to their sons but will always transmit them to their daughters. 

How is mitochondrial disease diagnosed? As 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. 

How does mitochondrial disease affect family members and future children? Depending on what type of mitochondrial disease you have, your siblings or future children may be at risk of developing mito. Passing on mito from parent to child depends on many factors, including whether the disease is caused by genetic mutations in the nuclear or mitochondrial DNA.

When a genetic diagnosis is made, healthcare teams and genetic counsellors will help determine if other family members are at risk and if that particular type of mito can be passed on to future children. You and your family may consider genetic testing and advise other family members to do the same. MitoCanada is here to provide you with all the resources you need. If you have questions about genetic counselling, reach out to us at info@mitocanada.org. 

What to do if there is no genetic diagnosis 

Genetic testing technology is advancing quickly, and testing options continue to improve. If you or your family members do not have a genetic diagnosis, talk to your healthcare team or a physician experienced in mito care. They can assist in the diagnosis process using clinical tests, laboratory evaluations, image studies and/or tissue biopsies. As is often a requirement, the tests referenced earlier in this guide must be completed first before a request for genetic testing is made. Genetic testing is costly. In some cases, tests are shipped out of province or country for processing. In certain provinces, genetic testing first requires provincial funding approval to receive coverage.

If genetic test results come back negative, you may still have a mitochondrial disease. Consider requesting another panel of genetic testing in the future. Genetic testing may be negative or inconclusive now, but in 3-5 year’s time may be able to determine a diagnosis. 

Currently, there is no cure for mitochondrial disease. Managing mito is an ongoing process; however, certain medications, supplements, exercise plans and nutrition management can help control and even ease some of the symptoms you may be experiencing. 

Medications: Treatment for mitochondrial disease is currently symptom-based management. Medications are quite variable and typically are used to treat the mito-associated symptoms (i.e. seizures, strokes).

Supplements: When considering the use of supplements, it is advised that you do so under the guidance of a healthcare provider, as speci!c supplements are chosen based on the type of mito you have been diagnosed with.

Many individuals with mito are prescribed the “mito cocktail.” This combination of supplements varies, depending on the condition being treated. Mito cocktail supplements may include creatine, L-carnitine, alpha-lipoic acid, riboflavin, and CoQ10. 

The best exercise for you is the exercise you enjoy doing! Mindful exercises can be highly beneficial for those with mito. Exercise can improve mitochondrial quantity and function, improve muscle strength, and help reduce fatigue. The benefits of exercise extend to every part of the body and improve mitochondrial health. 

To understand what types of exercise are safe for you and the frequency at which you should exercise, speak with your doctor. There are two main types of exercises to consider: endurance and resistance/strength. 

Endurance exercise, also known as aerobic exercise, involves many low-intensity repetitions that make your heart and lungs work harder. Some examples include walking, running, biking, jumping rope, swimming, treadmill, ski machine, Stairmaster, recumbent or upright bike (spinning), and pedal ergometer.

Resistance/strength exercise involves contracting muscles against resistance. Resistance can be your body weight or tools like dumbbells, rubber tubing, or items from around the house. It involves doing a low number of high-intensity repetitions. In the beginning, you may only be able to do one set. Over time, your goal is to do three sets of 12-15 repetitions of each exercise. Having an exercise buddy is a great way to stay motivated if you are new to exercise. 

Visit our Exercise as Medicine guide for more information and examples of endurance, resistance and balance exercises. 

It is important to listen to your body to exercise safely. Creating an exercise schedule can help you stay on track and ensure you have adequate time to rest. It is essential not to exhaust yourself. It is ok to take a break and recover, especially when you are new to exercise. Using a heart monitor is helpful to track your heart rate while exercising and can help ensure you stay within any recommended target zones. Pushing yourself too hard can lead to fatigue, which can be dangerous for people with mito. 

For children, find endurance and resistance exercises that are fun but appropriate for the type of mito they have. Modified and self-regulated physical education classes are beneficial, as exercises can be done at the child’s own pace. Pets such as dogs can be a great motivator for children to exercise. 

Be sure to watch for signs of fatigue or exhaustion.

Signs may include:

  • lightheadedness
  • severe muscle soreness
  • hearing loss
  • blurred vision
  • heart palpitations or chest pain
  • being unable to talk 

There are no specific mito diets or general dietary guidelines for mito patients. Instead, your dietary and nutritional needs will depend on the type of mito you have been diagnosed with and your current state of health. Maintaining a well-balanced diet, one rich in fruits, vegetables, grains, complex carbohydrates, proteins and healthy fats, is typically recommended. However, speak to your doctor to ensure you are including the foods best suited for your nutritional and mito needs.

Your doctor may recommend vitamins, multi-vitamins or iron. Many patients respond well to small, frequent meals throughout the day, and avoiding fasting. Restrictive diets like ketogenic, Atkins or low-carb diets are not advised and could worsen symptoms. If you do or plan to incorporate regular exercise into your weekly routine, it is important to pay attention to nutrition. Staying well-nourished will help with pre- and post- exercise recovery.

Here are some nutritional tips to consider when exercising:

  • Do not exercise after fasting for six or more hours
  • Always stay hydrated before, during and after your workouts
  • Have a light meal with carbohydrates before exercising
  • Keep fats, protein and fibre-dense foods low before exercising
  • After eating, wait at least 30 minutes before starting exercising
  • Try to have at least 20 grams of protein and carbohydrates within 30 minutes after exercising

Historically, it was thought that mito patients should avoid many medications as they could impact mitochondrial function. However, we now know that many medications are well-tolerated when taken for routine care. It is advised that caution be taken when using a new medication, and should any side effects be observed, reach out to your doctor as soon as possible. They will advise how to proceed with the treatment. Any time a patient is starting to use a new medication, they should take extra care to monitor any adverse symptoms that may develop. 

Valproic acid (brand name Depakote, Depakene)

  • This medication should be used with caution by patients with mitochondrial disease.
  • For POLG-related (mutation in POLG gene) disorders and mito disorders with liver involvement, it is advised not to take this medication. 

Anesthesia

  • It is essential to tell the anesthesiologist if you or your loved one has a mitochondrial disease.
  • Some mito patients may have anesthesia-related sensitivities. If this is the case, the patient may require a lower or adjusted dose when general anesthesia is required.
  • Muscle relaxants in anesthesia (also called neuromuscular blocking agents) should be monitored in patients with pre-existing myopathy or decreased respiratory drive (8). Generally, local anesthetics are well-tolerated. 

Antibiotics (aminoglycosides, linezolid, tetracycline, azithromycin and erythromycin)

  • Antibiotics such as aminoglycosides, linezolid, tetracycline, azithromycin and erythromycin should be avoided for patients with specific mitochondrial conditions. Ensure your physician knows your diagnosis.
  • If needed, these antibiotics should be taken with caution.
  • Most mito patients are fine with other antibiotics. 

Topiramate or Metformin

  • When using either of these two medications, it is recommended to monitor use.
  • Statins can sometimes worsen muscle weakness, monitor or avoid them. 

An emergency care plan should be created to ensure you receive the best medical care for your mito needs, when your medical team cannot be present. It may include plans for emergency room visits or hospital admissions. The emergency plan provides hospital staff with your medical history and emergency protocols to follow, such as a list of treatments you should receive while in hospital, lab work to complete, and medications to avoid. As every mito patient presents their disease differently, your patient emergency protocols will be different and personalized to meet your unique needs. 

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. 

Your Healthcare Team

Specialists involved in managing mito care include, but are not limited to: neurologists, geneticists, cardiologists, rheumatologists, epileptologists, physiatrists, dietitians, physiotherapists, orthopedic surgeons, audiologists, endocrinologists, immunologists, ophthalmologists and sleep medicine specialists (10). 

Even though you will have new specialists helping you manage your mito, it is strongly recommended that you keep your family doctor. Your family doctor should be able to care for your more complex medical needs and be willing to work alongside your specialists to continue providing care. 

MitoCanada has curated a provincial list of clinics that oversee the care of mito patients. 

View our metabolic clinic listing for province-specific information.

mitoLingo

Neurologist – a medical doctor who specializes in disorders of the brain and nervous system

Geneticist – a medical doctor who focuses on how genetic information is passed from parents to their children

Metabolic Specialist – a medical doctor who specializes in the processes that change food into energy to keep our cells healthy and working properly 

After receiving a mito diagnosis, many individuals may experience similar challenges and uncertainties as other newly diagnosed patients. With tests to rule out other conditions and tests to gather evidence that mito may be at play, the investigative process can heighten anxiety.

For newly diagnosed patients, the diagnosis can be a relief because testing is no longer needed and now there is a focus on treatment options to manage symptoms. However, patients and their families often also feel overwhelmed and concerned about ongoing care, disease progression, impacts on family life, and financial hardships.

While it is important to learn about your new diagnosis, you cannot learn everything overnight. Your specialists and clinic nurses are there to build your knowledge and confidence in living with mito, as well as guide you in management strategies. MitoCanada is here to provide you with resources, tools and guidance to help introduce you to a supportive Canadian mito community.

Many individuals and families reach out to professional counselling services pre- and post-diagnosis to help cope with the challenges they have faced and the stress, anger and sadness they experience. It may be helpful to talk to someone who can support you during this period of uncertainty. If you or your family feel overwhelmed, consider seeking support from a professional counsellor.

View MitoCanada’s list of provincial and national resources for emotional support. 

MitoCanada is dedicated to empowering and enhancing the lives of Canadians living with mitochondrial diseases. From advances in research to educational, and support programs to ways you can get involved in MitoCanada events, you can and a multitude of resources on our website:

Visit our Support Resources where you will and a Regional Resource page for financial, emotional, physical and social help and explore a health management app called Zamplo, a tool to track mito health history, appointments, test results, medications and more.

MitoCanda has created a Patient Contact Registry. This is a secure patient-populated database where individuals living with mito and their caregivers can share information about their lived experiences with mito and opt-in to be alerted about clinical trial opportunities in Canada.

All information entered into the registry is de-identified, meaning the information you share is private. Furthermore, entrusting MitoCanada with your lived-experience information helps ensure future patients and families will receive the guidance, education and support they need to live an optimal quality of life. 

By participating in the registry, you will:

  • Contribute to a growing understanding of mitochondrial disease in Canada.
  • Receive information and opportunities about clinical trials, which includes new drugs and therapies.
  • Help MitoCanada develop valuable education tools and resources.
  • Help strengthen our efforts in raising awareness and advocating for the needs of the Canadian mitochondrial community to provincial and federal governments. 

Clinical trials can be a fantastic opportunity to advance research and medicine. By volunteering in a clinical trial, you may have the opportunity to access medications that may positively impact your disease. Your involvement, first-hand experiences, and the perspectives you share in a trial all help bring a new treatment to Canada that improves quality of life. These elements can impact the health and lives of future mito patients. The truth is, patient participation is essential to clinical trials. Your time and involvement matter! 

Clinical trials are controlled research studies that investigate the safety and efficacy of either a new drug treatment, device or procedure. A clinical trial study goes through an extensive research process and must gain approval from Health Canada before moving to patient trials. Once approved by Health Canada, a trial is then done in phases, in which a clinical trial team tests the safety and effectiveness of a new drug or device in different populations. Throughout each trial phase, reviews are completed and approvals are required to ensure a trial is conducted properly and are in the best interests of participants. 

Watch “Clinical Trials Explained for Kids”, an animation which shares an excellent overview of clinical trials and walks you through the consent (ascent) process in a friendly, upbeat and entertaining way. MitoCanada is here to support you throughout the clinical trial process and to answer any questions you may have.

MitoCanada provides updated lists of clinical trial opportunities for Canadians. Visit our dedicated page to find clinical trials. 

Learn more about clinical trials by viewing our web presentation: Understanding Clinical Trials, the Patient Perspective 

1. Sulaiman SA, Mohd Rani Z, Mohd Radin FZ, Abdul Murad NA. Advancement in the diagnosis of mito-chondrial diseases. J Transl Genet Genom 2020;4:159-87.

2. Bainbridge, Laura. “Understanding and Coping with Mitochondrial Disease.” McMaster Children’s Hospital, Hamilton Health Sciences, 18 Aug. 2010, pg3.

3. Bainbridge, Laura. “Understanding and Coping with Mitochondrial Disease.” McMaster Children’s Hospital, Hamilton Health Sciences, 18 Aug. 2010, pg4.

4. Bainbridge, Laura. “Understanding and Coping with Mitochondrial Disease.” McMaster Children’s Hospital, Hamilton Health Sciences, 18 Aug. 2010, pg4.

5. Bainbridge, Laura. “Understanding and Coping with Mitochondrial Disease.” McMaster Children’s Hospital, Hamilton Health Sciences, 18 Aug. 2010, pg5.

6. Bainbridge, Laura. “Understanding and Coping with Mitochondrial Disease.” McMaster Children’s Hospital, Hamilton Health Sciences, 18 Aug. 2010, pg6.

7. Bainbridge, Laura. “Understanding and Coping with Mitochondrial Disease.” McMaster Children’s Hospital, Hamilton Health Sciences, 18 Aug. 2010, pg6.

8. Parikh, Sumit, et al. “Diagnosis and Management of Mitochondrial Disease: A Consensus Statement from the Mitochondrial Medicine Society.” Genetics in Medicine, 11 Dec. 2014, pp. 1–13.

9. Parikh, Sumit, et al. “Diagnosis and Management of Mitochondrial Disease: A Consensus Statement from the Mitochondrial Medicine Society.” Genetics in Medicine, 11 Dec. 2014, pp. 1–13.

10. Parikh, Sumit et al. “Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society.” Genetics in medicine: o$cial journal of the American College of Med-ical Genetics vol. 19(12),2017. Critical Care Services Ontario. “Rare Diseases Working Group Report”. 10 Mar. 2017.

11. Colombo, Maria & Botto, Nicoletta & Vittorini, Simona & Paradossi, Umberto & Andreassi, Maria Grazia. (2009). Clinical utility of genetic tests for inherited hypertrophic and dilated cardiomyopathies. Cardiovascu-lar ultra-sound. 6. 62. 10.1186/1476-7120-6-62.

Citation: Mitochondrial Care Network, “A Guide for the Newly Diagnosed” 2019