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Friedreich ataxia
This condition is caused by genetic changes in the FXN gene, resulting in reduced production of a vital protein called frataxin. It leads to progressive nerve damage and affects approximately 1 in 50,000 people.
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Overview
Friedreich ataxia is a genetic disorder that progressively affects the nervous system, leading to symptoms such as loss of balance, uncoordinated movements, and speech difficulties [PMID:29668856]. It is a rare condition, affecting approximately 1 in 50,000 people in the general population. Symptoms typically begin in childhood or adolescence, although later onset forms are also recognised. The condition is progressive, meaning symptoms tend to worsen over time.
Over time, Friedreich ataxia can affect various body systems beyond the nervous system, including the heart and the endocrine system. The severity and progression of the condition can vary significantly among individuals, even within the same family. Ongoing research aims to better understand the disease mechanisms and develop effective treatments.
Symptoms & clinical features
The initial symptoms of Friedreich ataxia often involve problems with coordination and balance, known as ataxia. Individuals may experience an unsteady gait, difficulty with fine motor skills, and frequent falls. Speech can become slurred (dysarthria), and there may be difficulties with swallowing (dysphagia) as the condition progresses [PMID:29668856].
Beyond these neurological symptoms, Friedreich ataxia can also affect other parts of the body. Many individuals develop a heart condition called hypertrophic cardiomyopathy, where the heart muscle thickens. Other common features include curvature of the spine (scoliosis) and foot deformities. Some individuals may also develop diabetes mellitus [PMID:29668856]. Vision and hearing can sometimes be affected, and muscle weakness can become more pronounced over time.
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Affected organs
Friedreich ataxia predominantly affects the nervous system, particularly nerve pathways in the spinal cord and the cerebellum, which is the part of the brain responsible for coordinating voluntary movements. The peripheral nerves, which send signals from the brain and spinal cord to the rest of the body, are also typically affected.
In addition to the central and peripheral nervous systems, the heart is commonly affected, with hypertrophic cardiomyopathy being a frequent complication. The pancreas can also be implicated, leading to an increased risk of developing diabetes. Bone structure, particularly in the spine and feet, can be impacted, leading to conditions like scoliosis and pes cavus (high-arched feet).
Risks & severity
Friedreich ataxia is a progressive condition, meaning symptoms generally worsen over time, though the rate of progression varies considerably between individuals. Most people experience initial symptoms between the ages of 5 and 15 years, but onset can range from early childhood to adulthood. The condition can lead to significant disability, with many individuals eventually requiring a wheelchair [PMID:29668856].
The severity of Friedreich ataxia is influenced by the genetic change in the FXN gene, with larger expansions often correlating with earlier onset and more rapid progression. Complications such as severe heart disease or diabetes can also impact the overall health and prognosis. Regular monitoring and supportive care are important for managing the condition and its associated risks.
Genetic causes
Friedreich ataxia is caused by changes in a gene called FXN, which provides instructions for making a protein known as frataxin [PMID:33671887]. Frataxin is crucial for the normal function of mitochondria, which are often called the 'powerhouses' of our cells, as they produce energy. Specifically, frataxin plays a vital role in the assembly of iron-sulfur clusters, essential components of many proteins involved in energy production and protection against cellular damage.
In most cases of Friedreich ataxia, the genetic change involves an expansion of a trinucleotide repeat sequence (GAA) within the FXN gene. This expansion leads to a significant reduction in the amount of functional frataxin protein produced. Without enough frataxin, mitochondrial function is impaired, leading to a build-up of iron and increased oxidative stress, which causes damage to nerve cells and other tissues, particularly in the heart and pancreas [PMID:33671887]. Some individuals may have a GAA expansion on one copy of the gene and a different type of pathogenic variant (e.g., a point mutation) on the other copy.
- FXN frataxinThe FXN gene provides instructions for making the frataxin protein, which is primarily located in the mitochondria and plays a role in iron-sulphur cluster assembly.
Inheritance pattern
Friedreich ataxia is inherited in an autosomal recessive pattern. This means that a person must inherit two altered copies of the FXN gene - one from each parent - to develop the condition. Individuals who inherit only one altered copy of the FXN gene from one parent are known as carriers. Carriers typically do not show symptoms of Friedreich ataxia because their single working copy of the FXN gene produces enough frataxin protein for normal cellular function.
When both parents are carriers of a pathogenic FXN gene alteration, there is a 25% chance with each pregnancy that their child will inherit two altered copies and develop Friedreich ataxia. There is a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit two unaffected copies and not be a carrier or have the condition. Genetic counselling can provide detailed information about inheritance patterns and risks for family members.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosing Friedreich ataxia typically begins with a clinical evaluation based on characteristic symptoms such as progressive ataxia, loss of reflexes, and other neurological and systemic signs. If Friedreich ataxia is suspected, a referral to a neurologist or a clinical geneticist is usually made.
The definitive diagnosis of Friedreich ataxia is confirmed through genetic testing, which looks for pathogenic changes in the FXN gene. This testing is available through the NHS Genomic Medicine Service (GMS) and is often accessed via specific R-codes, such as R328. A GP or specialist can refer patients for consideration of genetic testing, which involves a blood sample. Genetic counselling is an integral part of the diagnostic process, providing information and support to individuals and families regarding test results and their implications.
Management & lifestyle
While there is currently no cure for Friedreich ataxia, management focuses on alleviating symptoms, preventing complications, and improving quality of life. This often involves a multi-disciplinary team approach, including neurologists, cardiologists, physiotherapists, occupational therapists, and speech and language therapists.
Physiotherapy and occupational therapy can help maintain mobility, muscle strength, and fine motor skills. Speech therapy can address difficulties with communication and swallowing. Medications may be prescribed to manage specific symptoms or complications, such as heart problems or diabetes. Regular monitoring of cardiac function, blood glucose levels, and spinal curvature is important. Individuals and families can access support through NHS care pathways and patient organisations, connecting them with relevant services and resources.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like Friedreich ataxia can be referred to Clinical Genetics services within the NHS. Genetic testing for Friedreich ataxia (R-code R328) is available through the NHS Genomic Medicine Service following a clinical assessment by a specialist. A genetic counsellor can provide essential support throughout this process, explaining the implications of genetic test results and discussing family planning options. They also help navigate the broader NHS care pathway, ensuring access to appropriate specialist care and support groups.
Frequently asked questions
How does Friedreich ataxia typically progress?
Friedreich ataxia is a progressive condition, meaning symptoms gradually worsen over time. The rate of progression varies significantly among individuals, but it often leads to increased difficulty with walking, coordination, and can affect other organs like the heart.
Can carriers of Friedreich ataxia develop symptoms?
No, individuals who are carriers for Friedreich ataxia, meaning they have one altered copy of the FXN gene, typically do not develop symptoms of the condition. They have one functioning copy of the gene which produces enough frataxin protein to remain healthy.
What kind of support is available for individuals with Friedreich ataxia in the UK?
In the UK, individuals with Friedreich ataxia can access support through the NHS, including specialist clinics, physiotherapy, occupational therapy, and speech therapy. Genetic counselling is also available, and patient organisations can provide additional information and community support.
Are there any treatments for Friedreich ataxia?
Currently, there is no cure for Friedreich ataxia. However, management focuses on managing symptoms and complications, such as heart problems or diabetes, with medications and supportive therapies like physiotherapy to help maintain mobility and quality of life. Research into new treatments is ongoing.
When do symptoms of Friedreich ataxia usually start?
Symptoms of Friedreich ataxia often begin in childhood or adolescence, typically between the ages of 5 and 15 years. However, the age of onset can vary widely, with some people experiencing symptoms earlier or later in adulthood.