What is Friedreich ataxia?
Friedreich ataxia (FA) is a rare inherited disease that causes progressive damage to your nervous system and movement problems. Nerve fibers in your spinal cord and peripheral nerves degenerate, becoming thinner. (Peripheral nerves carry information from the brain to the body and from the body back to the brain and signal the muscles to generate movement.)
The cerebellum, part of your brain that coordinates balance and movement, also degenerates to a lesser extent. The disorder does not affect your thinking and reasoning abilities (cognitive functions). Symptoms typically begin between the ages of 5 and 15 years, although they sometimes appear after age 25.
Neurological symptoms of Friedreich ataxia may include:
- Awkward, unsteady movements and impaired muscle coordination (ataxia) that worsens over time
- Difficulty walking and poor balance (gait ataxia)
- Impaired sensory functions, such as loss of sensation in the arms and legs, which may spread to the trunk and other parts of the body
- Loss of normal reflexes, especially in the knees and ankles
- Slowness and slurring of speech (dysarthria)
- Increased muscle tone (spasticity)
- Curving of the spine to one side (scoliosis)
- Difficulty swallowing, due to difficulty coordinating the muscles of the tongue and throat
- Hearing and vision loss
FA may also cause heart disease and diabetes.
The rate of progression varies from person to person. Generally, within 10 to 20 years after the appearance of the first symptoms the person is confined to a wheelchair. Individuals may become completely incapacitated in later stages of the disease. There is no cure for the disorder. Friedreich ataxia can shorten life expectancy, and heart disease is the most common cause of death. However, some people with less severe features of FA live into their sixties or older.
Who is more likely to get Friedreich ataxia?
Although rare, Friedreich ataxia is the most common form of hereditary ataxia in the United States, affecting about one in every 50,000 people. Male and female children can inherit the disorder.
Friedreich ataxia is caused by a defect (mutation) in a gene labeled FXN, which carries the genetic code for the production of a protein called frataxin. Individuals who inherit two defective copies of the gene, one from each parent, will develop the disease. A person who inherits only one abnormal copy of the gene is called a carrier. A carrier will not develop the disease but could pass the gene mutation on to his or her children. About one in 90 Americans of European ancestry carries an abnormal FXN gene.
Frataxin is found in the energy-producing parts of the cell called mitochondria. In FA, an abnormal pattern in the DNA sequence of the protein (called a triplet repeat) appears hundreds or more times, which greatly disrupts the normal production of frataxin. (In FA, the triplet repeat is guanine-adenine-adenine, or GAA.) Research suggests that without a normal level of frataxin, certain cells in the body (especially peripheral nerve, spinal cord, brain, and heart muscle cells) produce energy less effectively and have been hypothesized to have a buildup of toxic byproducts leading to what is called “oxidative stress.” Lack of normal levels of frataxin also may lead to increased levels of iron in the mitochondria. When the excess iron reacts with oxygen, free radicals can be produced. Although free radicals are essential molecules in the body metabolism, they can also destroy cells and harm the body.
A triplet repeat expansion has been implicated as the cause of several diseases in which a person needs to inherit only one abnormal gene. Friedreich ataxia is the only known genetic disorder that requires inheriting two copies of the abnormal FXN gene to cause the disease.
How is Friedreich ataxia diagnosed and treated?
Diagnosing Friedreich ataxia
A diagnosis of Friedreich ataxia requires a careful clinical examination, which includes a medical history and a thorough physical exam, in particular looking for balance difficulty, loss of joint sensation (proprioception), absence of reflexes, and signs of neurological problems. Genetic testing now provides a conclusive diagnosis. Other tests that may aid in the diagnosis or management of the disorder include:
- Electromyogram (EMG), which measures the electrical activity of muscle cells
- Nerve conduction studies, which measure the speed with which nerves transmit impulses
- Electrocardiogram (also called EKG or ECG), which gives a graphic presentation of the electrical activity or beat pattern of the heart
- Echocardiogram, which records the position and motion of the heart muscle
- Blood tests to check for elevated glucose levels and vitamin E levels
- Magnetic resonance imaging (MRI) or computed tomography (CT) scans, tests which provide brain and spinal cord images that are useful for ruling out other neurological conditions
Treating Friedreich ataxia
As with many degenerative diseases of the nervous system, there is currently no cure or effective treatment for Friedreich ataxia. However, many of the symptoms and accompanying complications can be treated to help individuals maintain optimal functioning as long as possible. A multi-specialty team approach is essential to the treatment of someone with FA. Doctors can prescribe treatments for diabetes, if present; some of the heart problems can be treated with medication as well. Orthopedic problems such as foot deformities and scoliosis can be corrected with braces or surgery. Physical therapy may prolong use of the arms and legs. Swallowing and speech issues should be followed closely. Hearing impairment can be helped with hearing aids.
Genetic testing is essential for proper clinical diagnosis and can aid in prenatal diagnosis and determining a person carrier status. Genetic counselors can help explain how Friedreich ataxia is inherited.
A primary care physician can screen people for complications such as heart disease, diabetes, and scoliosis, and can refer individuals to specialists such as cardiologists, physical therapists, and speech therapists to help deal with some of the other associated problems.
Support and information for families is also available through a number of private organizations. These groups can offer ways to network and communicate with others affected by FA. They can also provide access to patient registries, clinical trials information, and other useful resources.
What are the latest updates on Friedreich ataxia?
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world.
The range of NIH-funded research on Friedreich ataxia (FA) includes determining what causes the gene mutation and how it functions, gaining a better understanding of frataxin, and investigating ways to override the genetic mutation and to develop treatments for the disease. In addition to NINDS, several other Institutes and Centers of the NIH support research on Friedreich ataxia.
Researchers hope to define the mechanisms involved in the silencing of the FXN gene, which could reveal potential ways to restore normal gene function. One approach is to use induced pluripotent stem cell (iPSC) lines that have been turned into (an action called derived) neuronal cells as a model system to study the mechanisms of gene expression changes and FXN gene silencing. (iPSCs are a type of stem cell that can be derived from skin or blood cells and be activated to become other types of cells of the body.)
Other research efforts include a better understanding of the mitochondrial defects associated with the disease, developing new animal models of Friedreich ataxia that closely mimic the gene mutations found in people affected by the disease, and developing biomarkers (signs that can indicate the diagnosis or progression of a disease) for future clinical trials.
In addition, a project of the Therapeutics for Rare and Neglected Diseases program of the NIH's National Center for Advancing Translational Sciences (NCATS) is seeking to develop a protein replacement therapy for Friedreich ataxia that uses a new technology to deliver functional frataxin protein to mitochondria.
More information about Friedreich ataxia research supported by NINDS and other NIH Institutes and Centers can be found using NIH RePORTER, a searchable database of current and past research projects supported by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects. For research articles and summaries on Friedreich ataxia, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one help improve care for people with Friedreich ataxia?
Consider participating in a clinical trial so clinicians and scientists can learn more about Friedreich ataxia. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.
All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with FA at Clinicaltrials.gov, a searchable database of current and past clinical studies and research results.
Where can I find more information on Friedreich ataxia?
The following organizations and resources can help individuals, families, friends, and caregivers of people living with Friedreich ataxia:
Friedreich's Ataxia Research Alliance (FARA)
Muscular Dystrophy Association
National Ataxia Foundation (NAF)
Information about FA is also available:
Phone: 202-966-5557 or 800-336-4363
National Organization for Rare Disorders (NORD)
Phone: 203-744-0100 or 800-999-6673