FA occurs in approximately 1 in 40,000 people. It is the most common form of hereditary ataxia in Europe, the Middle East, South Asia, and North Africa. Both male and female children can inherit FA.

FA is caused by a mutation in the FXN gene, which provides instructions for the production of a protein called frataxin. This protein is needed for the functioning of mitochondria, which are the energy-producing parts of cells. As individuals with FA have both copies of the FXN gene affected, they do not produce adequate amounts of frataxin. Consequently, tissues in the body that are especially dependent on cellular energy production, such as nerve and heart cells, start to degenerate. 

In most individuals affected by FA, there is a very specific error in the FXN gene called an expanded GAA trinucleotide repeat. Every gene is made up of different arrangements of four chemical units (nucleotides) called adenine (A), cytosine (C), guanine (G), and thymine (T). In most individuals with FA, both copies of the FXN gene contain abnormally long tracts of repeating units that contain guanine-adenine-adenine (GAA trinucleotide repeat). In contrast to individuals without FA who have less than 30 GAA repeats, individuals with FA typically have expanded tracts that range from 100 to 1300 repeats in both copies of the FXN gene. This expanded GAA repeat mutation causes gene silencing and impairs the production of frataxin protein. The severity of the FXN gene silencing depends on the length of the expanded GAA repeat mutation and this is also correlated with the variability of associated symptoms. An affected individual with shorter expansions, such as less than 400 GAA repeats, may have a later age of onset, slower progression of clinical features, and milder cardiomyopathy (e.g. heart problems). FA is the only known genetic disorder that requires an individual to inherit two copies of the abnormal FXN gene to be affected. Nearly all individuals with FA (98%) have two copies of this trinucleotide repeat abnormal form of FXN, but about 2% of affected individuals have other defects in the gene that cause FA. 

Symptoms of FA typically begin in children between the ages of 5 and 15 years, but may also occur later in adulthood. The primary symptom and typically the first neurological symptom to appear is difficulty walking and poor muscle coordination/balance (ataxia). As FA can affect all muscles, those involved in the mouth and throat are often affected leading to slurred speech and impaired swallowing. Speech may also become hesitant and jerky. As the condition gradually worsens, the ataxia will spread affecting the arms and torso. The curving of the spine to one side called scoliosis occurs in up to two-thirds of affected individuals and often requires treatment. FA often affects the heart muscle in various forms ranging from mild abnormalities to life-threatening problems, including enlargement of the heart (hypertrophic cardiomyopathy) and a fast heart rate (tachycardia). Diabetes is also common affecting around 30% of individuals with FA. 

FA is typically suspected in an individual following a clinical examination and a diagnosis is then confirmed with molecular genetic testing to identify mutations in the FXN gene. A thorough physical examination will assess areas including any balance difficulties, loss of joint sensation, and signs of neurological problems.

Tests to confirm FA diagnosis include:

• Electromyogram (EMG) that measures the electrical activity of muscle cells

• Electrocardiogram (EKG or ECG) that provides a graphic presentation of the electrical activity of beat pattern of the heart

• Echocardiogram that records the position and motion of the heart

• Nerve conduction studies to see how quickly the nerves transmit impulses

• Blood tests, particularly to check for elevated glucose levels to screen for diabetes

• Magnetic resonance imaging (MRI) or computed tomography (CT) scans to provide brain and spinal cord images that can help to determine any neurological conditions or problems

There is currently no cure or effective treatment for FA. However, many of the associated symptoms and complications can be treated or managed effectively. A multidisciplinary treatment strategy tends to be the most appropriate approach as FA affects multiple areas of the body. Prostheses, walking aids, wheelchairs and physical therapy can enable mobility and orthopedic surgery or non-surgical interventions may be used to treat scoliosis along with any abnormalities in the feet. Heart problems and diabetes may be treated with medication and dietary modifications may also be advised. Speech therapy can help to improve verbal communication. Continuous medical supervision is recommended to oversee management and treatment of potential complications that may involve the heart, spine, muscles, vision and hearing. 

The rate of FA progression varies across individuals. Many are confined to a wheelchair within 10 to 20 years after the first symptoms of FA appear. The condition can shorten life expectancy, and the most common cause of death is heart disease. However, many affected individuals can lead active lives, go on to have families and in some cases, live much longer into their sixties and older.

Useful information and resources can be found here: https://curefa.org/ 

National Institute of Neurological Disorders and Strokes. Freidreich Ataxia Fact Sheet. 2018. Available from: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Friedreichs-Ataxia-Fact-Sheet

National Organization for Rare Disorders. Friedreich’s Ataxia. 2018. Available from: https://rarediseases.org/rare-diseases/friedreichs-ataxia/

Muscular Dystrophy Association. Friedreich’s Ataxia (FA). n.d. Available from: https://www.mda.org/disease/friedreichs-ataxia