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Mitochondrial Disorder Medical Information

Visit the BCMJ May 2011 issue here to read a compilation of medical articles about mitochondrial disease.

What are mitochondria?
A mitochondrion (singular of mitochondria) is part of every cell in the body that contains genetic material. Mitochondria are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions. Mitochondria produce energy in the form of adenosine triphosphate (ATP), which is then transported to the cytoplasm of a cell for use in numerous cell functions.


What are mitochondrial and metabolic diseases?
Mitochondrial medicine is a new and rapidly developing medical subspecialty. Many specialists are involved in researching mitochondrial diseases, including doctors specializing in metabolic diseases, cell biologists, molecular geneticists, neurologists, biochemists, pathologists, immunologists, and embryologists. 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.

Mitochondrial and metabolic medical conditions are now referred to as mitochondrial cytopathies. Mitochondrial cytopathies actually include more than 40 different identified diseases that have different genetic features. The common factor among these diseases is that the mitochondria are unable to completely burn food and oxygen in order to generate energy.

The process of converting food and oxygen (fuel) into energy requires hundreds of chemical reactions, and each chemical reaction must run almost perfectly in order to have a continuous supply of energy. When one or more components of these chemical reactions does not run perfectly, there is an energy crisis, and the cells cannot function normally. As a result, the incompletely burned food might accumulate as poison inside the body. 

This poison can stop other chemical reactions that are important for the cells to survive, making the energy crisis even worse. In addition, these poisons can act as free radicals (reactive substances that readily form harmful compounds with other molecules) that can damage the mitochondria over time, causing damage that cannot be reversed. Unlike nuclear DNA, mitochondrial DNA has very limited repair abilities and almost no protective capacity to shield the mitochondria from free radical damage.


What are the symptoms of mitochondrial diseases?
The types of mitochondrial diseases are categorized according to the organ systems affected and symptoms present. Mitochondrial diseases might affect the cells of the brain, nerves (including the nerves to the stomach and intestines), muscles, kidneys, heart, liver, eyes, ears, or pancreas. In some patients, only one organ is affected, while in other patients all the organs are involved. Depending on how severe the mitochondrial disorder is, the illness can range in severity from mild to fatal.

Depending on which cells of the body are affected, symptoms might include:

  • Poor growth
  • Loss of muscle coordination, muscle weakness
  • Visual and/or hearing problems
  • Developmental delays, learning disabilities
  • Mental retardation
  • Heart, liver, or kidney disease
  • Gastrointestinal disorders, severe constipation
  • Respiratory disorders
  • Diabetes
  • Increased risk of infection
  • Neurological problems, seizures
  • Thyroid dysfunction
  • Dementia (mental disorder characterized by confusion, disorientation, and memory loss)


How common are mitochondrial diseases?
About one in 4,000 children in the United States will develop mitochondrial disease by the age of 10 years. One thousand to 4,000 children per year in the United Sates are born with a type of mitochondrial disease.

In adults, many diseases of aging have been found to have defects of mitochondrial function. These include, but are not limited to, type 2 diabetes, Parkinson's disease, atherosclerotic heart disease, stroke, Alzheimer's disease, and cancer. In addition, many medicines can injure the mitochondria.


What causes mitochondrial disease?
For many patients, mitochondrial disease is an inherited condition that runs in families (genetic). 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 predict the risk of recurrence for future children.

The types of mitochondrial disease inheritance include:

  • nDNA (DNA contained in the nucleus of the cell) inheritance. Also called autosomal inheritance.
    -- If this gene trait is recessive (one gene from each parent), often no other family members appear to be affected. There is a 25 percent chance of the trait occurring in other siblings.
    -- If this gene trait is dominant (a gene from either parent), the disease often occurs in other family members. There is a 50 percent chance of the trait occurring in other siblings.
  • mtDNA (DNA contained in the mitochondria) inheritance.
    -- 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.
  • Combination of mtDNA and nDNA defects:
    -- Relationship between nDNA and mtDNA and their correlation in mitochondrial formation is unknown
  • Random occurrences
    Diseases specifically from deletions of large parts of the mitochondrial DNA molecule are usually sporadic without affecting other family member
    -- Medicines or other toxic substances can trigger mitochondrial disease


How are mitochondrial diseases diagnosed?
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.

Under ideal circumstances, the evaluation will produce an answer. However, even after a complete evaluation, the doctor might not be able to confirm a specific diagnosis or put a name to the disorder. In many cases, however, the physician will be able to identify which patients do and don't have metabolic diseases.

Mitochondrial disease is diagnosed 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 and recommended by your doctor.


How are mitochondrial diseases treated?
There are no cures for mitochondrial diseases, but treatment can help reduce symptoms, or delay or prevent the progression of the disease.

Treatment is individualized for each patient, as doctors specializing in metabolic diseases have found that every child and adult is "biochemically different." That means that no two people will respond to a particular treatment in a specific way, even if they have the same disease.

  • Certain vitamin and enzyme therapies, along with occupational and physical therapy, might be helpful for some patients.

Vitamins and supplements prescribed might include:

- Coenzyme Q10
- B complex vitamins: thiamine (B1), riboflavin (B2), niacin (B3), B6, folate, B12, biotin, pantothenic acid
- Vitamin E, lipoic acid, selinium, and other antioxidants
- L-carnitine (Carnitor®)
- Intercurrent illness supplement: vitamin C, biotin

  • Diet therapy, as prescribed by your doctor along with a registered dietitian, might be recommended.
  • Antioxidant treatments as protective substances are currently being investigated as another potential treatment method.

Important: Specific treatments should always be guided by a metabolic specialist. Patients should not take any of these supplements or try any of the treatments unless prescribed by a doctor. Taking inappropriate supplements or treatments might lead to delays or failure in establishing an accurate diagnosis.


What is the prognosis or outlook?
Once a patient is diagnosed with a specific mitochondrial disease, the patient's medical problems have already been identified or can be identified with proper testing so treatment can be initiated to relieve symptoms and delay the progression of the disease.

There is no way to predict the course of mitochondrial diseases. They might progress quickly or slowly, even over decades. The disease might also appear stable for years.

For parents considering having other children, genetic counseling is available. Although complex, prenatal testing is only available for a few types of mitochondrial disorders. Please discuss your concerns with your doctor.

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