Mitochondrial Disease Frequently Asked Questions (FAQs)

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, seizuresEpisodes of abnormal electrical activity in the brain., vision and/or hearing loss, gastrointestinalGI 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.

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.

• Mitochondrial failure causes cell injury that leads to cell death. When multiple organ cells die, organs begin to fail.
• 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.

The severity of mitochondrial disease symptoms is different from person to person. The most common symptoms are:

• Neuropsychological changes characterized by confusion, disorientation, dementiaLoss of cognitive functioning — thinking, remembering, and reasoning — to the extent that it interferes with a person's daily life, and memory loss
• 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
• Diabetes
• 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)

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 sclerosisA progressive nervous system disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control. (ALS), autoimmune disorders, environmental toxicities, and cancer.

For many patients, mitochondrial disease is an inherited genetic condition. Mutationsgenetic variant, genetic change 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 inheritanceThe way a genetic condition is passed down in a family. 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, often no 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 “carrierA person who has one copy of a genetic change. For many conditions, carriers do not show symptoms of a condition or their symptoms are less severe..” Carriers, like their parents, present healthy but could pass the mutation to their offspring.
• If the gene trait is dominantA gene from either parent which can express a disease., the disease may occur in other family members. There is a 50 percent chance of the trait occurring in other siblings/ offspring.
• Mitochondrial DNA (mtDNA) inheritance is contained in the mitochondria of the cell. There is a 100 percent chance of the trait occurring in other siblings because all of the mitochondria are inherited from the mother. Symptoms may be more or less severe due to heteroplasmyApplies to variants in mitochondrial DNA. Homoplasmy is the presence of only one variant, in a given mitochondrial gene, in an individual. Heteroplasmy is the presence in an individual of two more var. 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. It is believed that MtDNA and nDNA communicate with each other. Researchers think that such interactions may regulate the expression of particular sets of genes. This communication may explain how mitochondria are involved in cellular processes not related to energy generation, such as cell growth and death.

Random occurrences

• Medicines or other toxic substances can trigger mitochondrial disease.

Diseases specifically from deletions of large parts of the mtDNA molecule are usually sporadic without affecting other family members.

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 electroretinogramA diagnostic test that measures the electrical activity of the retina in response to a light stimulus. 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.

Misdiagnosis

Further progression of symptoms can occur if the symptoms are missed and opportunities for treatment and support are not recognized.

Lack of understanding of the disease and misinterpretation of symptoms can lead to misdiagnosis.

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, fatigueThe overall feeling of tiredness or lack of energy. It is not the same as simply feeling drowsy or sleepy. Being fatigued means having no motivation or energy., or poor nutrition, may lead to cell injury and associated worsening of baseline symptoms or the onset of new symptoms.

Exercise

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.

Vitamins and supplements prescribed typically include:

• Coenzyme Q10A relatively small fat-soluble organic (i.e., carbon-containing) molecule, found in membranes throughout the in the body. It readily transports both electrons and protons. Its many essential functions – ubiquinol preferred
• Alpha lipoic acidA small, vitamin-like organic molecule,made in the mitochondria, and found in every cell. It plays multiple essential roles. It is a necessary co-factor for the activity of five different enzyme compl
• RiboflavinIt is a type of vitamin B. It helps in red blood cell production and aids in the release of energy from proteins., and possibly other B vitamins
• Arginine – for stroke-like events
• Folinic acidReduced form of folic acid (vitamin B9). – 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 dietitianRegistered 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.

• 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 disease is inherited.

To connect with others facing the challenges of mitochondrial disease, visit the MitoAction closed Facebook group or join our weekly support calls.