Friedreich's Ataxia

Friedreich ataxia is a genetic condition that damages nerve tissue, causing a loss of muscle coordination (ataxia) that worsens over time. Other characteristics of this condition include the gradual loss of strength and sensation in the arms and legs, muscle stiffness (spasticity) in the limbs, and impaired speech. Friedreich ataxia may also affect heart function.

Types

25 percent of cases, however, occur after age 25. These cases are classified as late-onset Friedreich ataxia (LOFA), with onset between 26 and 39 years, or very late-onset Friedreich ataxia (VLOFA), which begins at age 40 or older.

Other Names

• FA
• FRDA
• Hereditary spinal ataxia
• Hereditary Spinal Sclerosis
• Spinocerebellar Ataxia, Friedreich

Signs and Symptoms

Typically, signs and symptoms of Friedreich ataxia first appear in childhood or the early teens. Poor balance when walking and slurred speech are often the initial symptoms. Most people with Friedreich's ataxia develop scoliosis (a curving of the spine to one side), which, if severe, may impair breathing. Other symptoms include chest pain, shortness of breath, and heart palpitations. ^[1]

Causes

Mutations in the FXN gene cause Friedreich ataxia.

The FXN gene provides instructions for making a protein called frataxin. Although its role is not fully understood, frataxin appears to be important for the normal function of energy-producing centers (mitochondria) within cells. Friedreich ataxia is caused by a mutation in which a DNA segment, known as the GAA triplet repeat, is abnormally expanded within the FXN gene. Normally, this segment is repeated 5 to 33 times within the FXN gene. In people with Friedreich ataxia, however, the GAA segment is repeated 66 to more than 1,000 times. The abnormally expanded GAA segment disrupts the production of frataxin, which severely reduces the amount of this protein in cells. Certain nerve and muscle cells cannot function properly with a shortage of frataxin, leading to the signs and symptoms of Friedreich ataxia.

Diagnosis

Doctors diagnose Friedreich's ataxia by performing a careful clinical examination, which includes a medical history and a thorough physical examination. Several tests may be performed, including electromyogram (EMG) and genetic testing. ^[2]

There is currently no effective cure or treatment for Friedreich's ataxia. However, many of the symptoms and accompanying complications can be treated to help patients maintain optimal functioning as long as possible. Diabetes and heart problems can be treated with medications. Orthopedic problems such as foot deformities and scoliosis can be treated with braces or surgery. Physical therapy may prolong use of the arms and legs. ^[3]

Chances of Developing Friedreich's Ataxia

Friedreich ataxia is estimated to affect 1 in 40,000 people.

Genetics

Mutations in the FXN gene cause Friedreich ataxia.

Heredity

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Research

Studies have revealed that frataxin, a protein that should normally be present in the nervous system, the heart, and the pancreas, is severely reduced in patients with Friedreich's ataxia. Studies have shown that patients have abnormally high levels of iron in their heart tissue. It is believed that the nervous system, heart, and pancreas may be particularly susceptible to damage from free radicals (produced when the excess iron reacts with oxygen) because once certain cells in these tissues are destroyed by free radicals they cannot be replaced. Nerve and muscle cells also have metabolic needs that may make them particularly vulnerable to free radical damage. The discovery of the genetic mutation that causes Friedreich's ataxia has added new impetus to research efforts on this disease. ^[4]

Expected Outcome

Generally, within 15 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease, individuals become completely incapacitated. Most people with Friedreich's ataxia die in early adulthood if there is significant heart disease, the most common cause of death. Some people with less severe symptoms live much longer. ^[5]

Other Resources

These resources address the management of Friedreich ataxia and may include treatment providers.

• MedlinePlus Encyclopedia: Friedreich's Ataxia
• Educational resources
• Patient support.
• MedlinePlus - Health information (2 links)
• Additional NIH Resources - National Institutes of Health (3 links)
• Educational resources - Information pages (3 links)
• Patient support - For patients and families (6 links)
• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature
• Online Books - Medical and science textsScriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID):Friedreich Ataxia and AVED
• OMIM - Genetic disorder catalog

References

1. ↑ Institute of Neurologial Disorders and Stroke, NIH
2. ↑ Institute of Neurologial Disorders and Stroke, NIH
3. ↑ Institute of Neurologial Disorders and Stroke, NIH
4. ↑ Institute of Neurologial Disorders and Stroke, NIH
5. ↑ Institute of Neurologial Disorders and Stroke, NIH