Mitochondrial disease is an inherited, chronic illness that can be present at birth or develop later in life. “Mito” is progressive and can cause physical, developmental, and cognitive disabilities. Symptoms can be mild, such as tiredness or weakness, or they can be severe, such as poor growth, loss of muscle coordination, muscle weakness and pain, seizures, vision and/or hearing loss, gastrointestinal issues, learning disabilities, and organ failure. Approximately 1 in 4,000 people have Mito. There is no cure, but there are treatments that can help with the symptoms.
What are Mitochondria?
• Mitochondria are tiny organelles found in every cell in the body except red blood cells. The number of mitochondria in a cell varies by tissue and cell type with higher numbers per cell found in high energy-requiring organs, such as the liver, heart, brain, muscles, pancreas, eyes, ears, kidney, and GI tract.
• Mitochondria are known as the “powerhouse of the cell.”
• Mitochondria are responsible for creating more than 90 percent of cellular energy which is necessary for the body to sustain life and support growth.
• Mitochondria turn nutrients into cellular energy in the respiratory chain cycle.
• Mitochondria have their own independent genome (mitochondrial DNA or mtDNA) that was likely derived from early bacteria.
• Mitochondrial failure causes cell injury that leads to cell death. When multiple organ cells die, organs begin to fail.
What is Mitochondrial Disease?
• Mitochondrial disease is a chronic, genetic disorder that occurs when the mitochondria of the cell fail to produce enough energy for cell or organ function.
• Many forms of mitochondrial disease are known, arising from defects in both the mtDNA and the cell’s nuclear DNA (nDNA).
• Mitochondrial disease can be inherited in a number of ways.
• Mitochondrial disease often presents very differently from individual to individual.
• One individual in a family or many individuals affected over a number of generations may be affected.
• Much of what we know about these diseases has been discovered since 1940. In 1962, the first patient was diagnosed with a mitochondrial disorder. In 1963, researchers discovered that mitochondria have their own DNA or “blueprint” (mtDNA), which is different than the nuclear DNA (nDNA) found in the cells’ nucleus.
What are the Symptoms of Mitochondrial Disease?
The severity of mitochondrial disease symptoms is different from person to person. The most common symptoms are:
• Poor growth and failure to thrive (in children)
• Loss of muscle coordination, muscle weakness and pain, low tone, exercise intolerance
• Neurological problems, seizures
• Autism, autistic spectrum, autism-like features
• Visual and/or hearing problems
• Developmental delays, learning disabilities
• Movement disorders
• Heart, liver or kidney disease
• Gastrointestinal disorders, including severe constipation, diarrhea, swallowing difficulty, repeated vomiting, cramping, reflux
• Increased risk of infection
• Neurological issues, including difficult to treat seizures, migraines, and stroke or stroke like events
• Thyroid and/or adrenal dysfunction
• Autonomic dysfunction (may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels
• Respiratory issues
• Lactic acidosis (the buildup of lactate in the body, which results in an excessively low pH in the bloodstream)
• Neuropsychological changes characterized by confusion, disorientation, dementia, and memory loss
How Common is Mitochondrial Disease?
• Infants, children, and adults may develop mitochondrial disorders. Experts in mitochondrial medicine describe a spectrum of disease, ranging from mild to severe. 1 in 4,000 people are estimated to have a genetically confirmed primary mitochondrial disease, yet many remain undiagnosed.
• In adults, many diseases of aging have been found to have defects of mitochondrial function, including, but not limited to, diabetes, Parkinson’s disease, Huntington’s disease, atherosclerotic heart disease, stroke, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), autoimmune disorders, environmental toxicities, and cancer.
What Causes Mitochondrial Disease?
• For many patients, mitochondrial disease is an inherited genetic condition. Mutations can also be spontaneous as well as be induced.
• A patient may be found to have a de novo variant, or new mutation, meaning that the mutation arose in this patient early in development and was not passed down from a parent or previous generations.
• An uncertain percentage of patients acquire symptoms due to other factors, including mitochondrial toxins.
It is important to determine which type of mitochondrial disease inheritance is present in order to pre- dict the risk of recurrence for future children. The types of mitochondrial disease inheritance include:
Nuclear DNA (nDNA) inheritance. nDNA is contained in the nucleus of the cell. This type of inheritance is also called autosomal inheritance.
• If the gene trait is recessive (one gene needed from each parent to have the disease), often no other family members appear to be affected. Two recessive mutations, one from each parent, are needed to express the disease. If parents both share the same recessive gene for a particular type of mitochondrial disease, 25% of children will get both mutated genes and have the disease, 25% will get no mutated genes and be healthy, and 50% will get a single mutation and be considered a “carrier,” like their parents, also be healthy, but could pass the mutation to their offspring.
• If the gene trait is dominant (a gene from either parent can express disease), the disease often oc- curs in other family members. There is a 50 percent chance of the trait occurring in other siblings/ offspring.
Mitochondrial DNA (mtDNA) inheritance. mtDNA is contained in the mitochondria of the cell.
• There is a 100 percent chance of the trait occurring in other siblings, since all mitochondria are inherited from the mother, although symptoms might be either more or less severe due to heteroplasmy (the percent of mutated cells). Higher rates of heteroplasmy are typically associated with more severe disease.
Combination of mtDNA and nDNA defects:
• The relationship between nDNA and mtDNA and their correlation in mitochondrial formation is a new area of study. MtDNA and nDNA communicate with each other. Researchers believe that such interactions may regulate the expression of particular sets of genes. This communication may ex- plain how mitochondria are involved in cellular processes not related to energy generation, such as cell growth and death.
• Diseases specifically from deletions of large parts of the mtDNA molecule are usually sporadic with- out affecting other family members.
• Medicines or other toxic substances can trigger mitochondrial disease.
How is Mitochondrial Disease Diagnosed?
• No reliable and consistent means of diagnosis currently exist. The road to diagnosis is often personalized based on symptoms. Clinicians are working to create diagnostic and treatment standards for mitochondrial medicine.
• Diagnosis can be made by DNA testing and/or muscle biopsy.
• Diagnosis of mitochondrial disease can be invasive, expensive, time-consuming, and labor-intensive. Therefore, evaluation is not taken lightly. Doctors experienced in diagnosing and treating these diseases will take either a step-wise approach to diagnosis or, in some centers, the evaluation takes place over a few days. The evaluation includes a combination of clinical observations and laboratory tests.
• Diagnosis can be made by:
Evaluating the patient’s family history
Performing a complete physical examination
Performing a neurological examination
Performing a metabolic examination that includes blood, urine, and optional cerebral spinal fluid tests
Performing other tests, depending on the patient’s specific condition and needs. These tests might include:
— Magnetic resonance imaging (MRI) or scan (MRS) if neurological symptoms are present
— Retinal exam or electroretinogram if vision symptoms are present
— Electrocardiogram (EKG) or echocardiogram if heart disease symptoms are present
— Audiogram or BAEP if hearing symptoms are present
— Blood test to detect thyroid dysfunction if thyroid problems are present
— Blood test to perform genetic DNA testing
More invasive tests, such as a skin or muscle biopsy, might be performed as needed.
• Lack of understanding of the disease and misinterpretation of symptoms can lead to misdiagnosis.
• Further progression of symptoms can occur if the symptoms are missed and opportunities for treatment and support are not recognized.
How is Mitochondrial Disease Treated?
Clinicians and researchers are working to develop therapies to treat and cure mitochondrial disease. Current treatments and therapies can help reduce symptoms, delay or prevent the progression of the disease. Even though a cure for mitochondrial disease has not been discovered, many clinical trials are under way to evaluate new therapies.
Physicians specializing in metabolic diseases have found that every child and adult is biochemically different, meaning that no two people will respond to a particular treatment in a specific way, even if they have the same disease. Therefore, treatment is individualized for each patient and type of mitochondrial disease.
Mitochondrial patients may become ill more quickly and more severely than other people because of a lower cellular reserve of energy. Cellular stresses, such as illness, fatigue, or poor nutrition, may lead to cell injury and associated worsening of baseline symptoms or the onset of new symptoms.
Research has shown that both endurance (such as running) and resistance (such as weight lifting) exercise can benefit patients with mitochondrial disease. Some benefits include an increase in mitochondrial health, antioxidant and muscle mitochondrial enzyme activity, oxygen uptake, and muscle strength, as well as improved clinical symptoms and a decrease in resting and post-exercise blood lactate levels.
The majority of research has shown exercise that is slowly increased can be safe for patients with mitochondrial diseases. Exercise should begin with short duration and low intensity. Exercise intolerance is common with mitochondrial disease, but even patients who have a difficult time exercising should still be encouraged to exercise beginning at their current level of function. Patients should consult their physician before beginning to exercise as cardiac or other evaluations may be needed. Physicians may recommend supervised progressive exercise aimed at improving function.
Treatment during illness
• Carry an emergency care plan that explains the disorder and management recommendations.
• Wear a Medic Alert bracelet or similar device.
• Take precautions to prevent prolonged fasting, including IV hydration for prolonged vomiting or other GI issues or fasting prior to procedures.
• IV hydration and/or lipids may be necessary for acute decompensation (organ failure from functional overload).
• Avoid, or use with caution: valproic acid, statins, metformin, high-dose acetaminophen, and selected antibiotics, including aminoglycosides, linezolid, tetracycline, azithromycin, and erythromycin. For a complete list of mito-toxic drugs, visit www.mitoaction.org/toxic
Vitamins and supplements prescribed typically include:
• Coenzyme Q10 – ubiquinol preferred
• Alpha lipoic acid
• Riboflavin, and possibly other B vitamins
• Arginine – for stroke-like events
• Folinic acid – only routine for documented CSF deficiencies and diseases known to cause deficiency and considered with central nervous system manifestations
• L-carnitine – for carnitine deficient patients only
• Vitamin C – for intercurrent illness supplement
Diet therapy, as prescribed by your doctor along with a registered dietitian, may be recommended.
Important: A physician should always guide specific treatments. Patients should not take any supplements or try any treatment unless prescribed by a doctor.
What are the Challenges of Living with Mitochondrial Disease?
• Mitochondrial disease can affect multiple organs, multiple family members, and multiple generations.
• Lack of awareness and understanding of the disease can delay treatment and diagnosis.
• Families are continuously forced to expend energy to explain their disease, advocate for themselves, and fight for services.
• Mitochondrial disease is often an “invisible disease.” On a good day, a patient may look fine and healthy, with more energy and appear rested. But on a bad day, patients can appear tired or even significantly ill. Repeated bad days may lead to decompensation and patients may have difficulty returning to baseline.
• Mitochondrial disease is unpredictable. Symptoms can vary day to day or even hour to hour.
• Mitochondrial disease is difficult to diagnose. Difficulties establishing a diagnosis interfere with a patient’s ability to obtain adequate recognition and appropriate medical care.
• An individual can become symptomatic at any time in life despite the fact that mitochondrial dis- ease is inherited.
To connect with others facing the challenges of mitochondrial disease, visit the MitoAction closed Facebook group or join our weekly support teleconferences.
What is the Prognosis for Someone with Mitochondrial Disease?
• The prognosis is variable. Some people live a normal life and are minimally affected; others can be severely compromised with the disease.
• The progression of mitochondrial disease is unpredictable and different for each person.