DEFINING FRIEDREICH’S ATAXIA
Friedreich’s ataxia (FA) is a genetic, progressive neuromuscular disease. People with FA experience issues with balance and coordination of movement that lead to life-altering loss of mobility. Other common symptoms can include fatigue, serious heart conditions, scoliosis, and diabetes. FA is life-shortening and affects an estimated 5,000 individuals in the United States and 15,000 worldwide.
All individuals with FA experience ataxia and neurological symptoms, but the severity and progression of these symptoms differ from person to person. Other symptoms also vary between individuals and are not always present. Different symptoms may appear over time, not necessarily all at once.
All people with FA experience ataxia, a loss of coordinated movement stemming from a disruption in the nervous system. It affects both fine and gross motor skills. What begins as difficulty with balance or clumsiness progresses to difficulty performing everyday activities.
People with FA may have cardiomyopathy (abnormal thickening of the heart muscle) or cardiac arrhythmias (abnormal heart rhythm). Initially, these heart conditions may not cause symptoms but can be detected through cardiac tests. Heart conditions are the main cause of mortality in FA.
About 70% of people with FA have scoliosis, or sideways curvature of the spine. In some individuals this can progress and require corrective surgery.
People with FA can develop diabetes. This can present in childhood or adulthood. It is important to get regular screening because it can be managed with standard treatment approaches.
Fatigue impacts most people with FA. More than just general tiredness, fatigue is a type of exhaustion that can affect everyday activities.
Over time, people with FA may develop slurred speech, called dysarthria. This can cause difficulty with communication.
While not typically present at time of diagnosis, people with FA can develop loss of peripheral, central, and color vision over time. Vision impairment with FA has impact on quality of life.
People with FA can develop hearing impairment. In particular, people with FA may have difficulty understanding the speech of others, especially in a noisy environment. This symptom is not usually present at the time of diagnosis.
Other signs and symptoms of FA include low body mass index (BMI), muscle pain or stiffness, dysphagia (difficulty swallowing), urinary frequency or urgency, osteoporosis (low bone density), pes cavus (high arched feet), sleep apnea, extra eye movements, and depression/anxiety. For more in-depth information about FA signs and symptoms, visit the Clinical Management Guidelines.
FA is a genetic disease, which means genetic testing is the gold standard for diagnosis. The genetic test will examine the causative gene in FA, FXN.
Most people begin experiencing symptoms and receive a diagnosis between the ages of 5 and 15 years. About 25% of people have late onset FA, and they begin experiencing symptoms in adulthood.
Each person with FA has a different journey that leads them to a genetic diagnosis. Click below to read more.
Most people begin their diagnostic journey because they notice symptoms associated with the onset of ataxia. These symptoms can look like clumsiness, frequent falling, difficulty keeping up with friends when walking or playing, or a decline in athletic ability. For other people, their first symptom might be hypertrophic cardiomyopathy or scoliosis. The first step on this journey is usually a visit with a primary care provider — your pediatrician or family doctor. The primary care provider will then refer you to a specialist such as a neurologist or cardiologist for an in-depth evaluation of these symptoms.
In children, it can be difficult to distinguish neurological symptoms from the wide range of developmental abilities or time to acquire certain motor milestones. This can lead to delays in referrals to a specialist and slow down the diagnostic journey.
A visit with a neurologist will include several different tests that will help them understand what your symptoms are and why they might be occurring. These tests can be as simple as the neurologist watching you walk down the hallway, touch your own nose, or reach out to grab an object. The neurologist will also ask you for a history of your symptoms and test your reflexes. Some clues that might make the neurologist consider FA as an answer for your symptoms are a unique gait or walking pattern, more difficulty performing tasks with eyes closed, or a lack of reflexes.
It is not uncommon for a neurologist to do specialized testing of your nerves, such as nerve conduction testing or MRI of the brain and spinal cord.
If your neurologist has a suspicion that FA is the cause for your symptoms, they may give you a clinical diagnosis of FA. A clinical diagnosis is based upon signs and symptoms of the disease without confirmatory genetic testing. A clinical suspicion or diagnosis of FA should always be confirmed with genetic testing.
If your doctor is concerned you have FA based on your symptoms and medical history, they will order a test that examines the FXN gene. Mutations, or genetic changes, in this gene are what cause FA. You can learn more about the genetics of FA further down on this page.
The laboratory performing the test will need a sample of your DNA which can come from a blood or saliva sample, depending on the lab. It will likely take a few weeks for the results of the test to come back.
A positive test result means that you have an official diagnosis of FA. Learn more about next steps through the Managing FA page.
Click below to learn about what a negative test result could mean.
If you are having trouble accessing genetic testing or have questions about genetic testing, a genetic counselor might be able to help.
Sometimes a doctor may suspect someone has FA, but the genetic test for FA is negative.
This might be because this individual truly does have FA, but the genetic test was unable to detect their specific FXN mutation. This occurs in up to 5% of people with FA. You can learn more about different FA mutations in the guides for newly diagnosed individuals and families. If you are concerned that you have FA but your genetic test was negative, have your doctor read about genetic tests for FA to determine if an additional genetic test for FA is needed. You could also seek advice from a geneticist or genetic counselor, healthcare professionals with expertise in ordering genetic tests.
Other times, someone with suspected FA has a negative genetic test because they don’t have FA. Instead, they have a disease that has symptoms similar to FA, but a different genetic cause. Click below to read about diseases similar to FA.
Here are some diseases that have overlapping symptoms with FA:
It is possible for someone to be initially diagnosed with FA, but, when genetic testing for FA is negative, these other conditions should be considered.
It is also possible for someone to be initially misdiagnosed with one of these conditions and then later find out that it is FA causing their symptoms. For example, when neurological symptoms begin in teens and young adults, the neurologist might initially consider a diagnosis of Charcot Marie Tooth (CMT) disease but then as symptoms progress or if genetic testing for CMT is negative, an FA diagnosis may be pursued.
About 5% of people, especially young children, are diagnosed with FA after receiving a diagnosis of cardiomyopathy. Cardiomyopathy might present as difficulty breathing, exercise intolerance, or a heart murmur that leads to cardiac testing. A visit with a cardiologist will entail several tests that evaluate the structure and function of the heart. An echocardiogram, or ultrasound of the heart, can detect cardiomyopathy, or the abnormal thickening of the heart muscle. FA is one of many genetic conditions that can cause cardiomyopathy. After a diagnosis of cardiomyopathy, an evaluation of neurological signs and symptoms along with genetic testing may lead to an FA diagnosis.
Frataxin is used by the mitochondria, the energy generating components of cells. Within the mitochondria, normal levels of frataxin support energy production and protect against cellular damage. Mutations in the FXN gene lead to poor production of frataxin. This results in cellular damage and poor production of cellular energy, leading to the signs and symptoms of FA.
Even though FA is a genetic condition it is often the case that there is no known family history of FA when someone is diagnosed.
Humans have two copies of each gene. In a recessive disease like FA, an affected person inherits two mutated copies of the FXN gene, one from each parent. The parents are called carriers. They have one normal copy of the FXN gene and one mutated copy. Carriers do not have symptoms of FA or develop the disease.
In the United States, it is estimated that 1 in every 100 or 1% of people are carriers of FA. If two carriers have children, each of their children has a 1 in 4, or 25%, chance of having FA. If someone with FA has children, the chance of their children also having FA depends on whether their partner is a carrier or also affected by FA. If you have questions about inheritance or the chances of your family members inheriting FA, talk to your health care provider or a genetic counselor.
Most people with FA have the same mutation on their FXN genes: a triplet repeat expansion. All genes are composed of a genetic alphabet containing 4 letters: C, G, A, and T. The spelling of the FXN gene includes a repetition of the three letters “GAA.” People unaffected by FA usually have between 7 and 30 GAA repeats in the FXN gene. FA is caused when this stretch of GAA’s is expanded, usually to over 100 repeats. Higher numbers of repetitions have been linked to earlier age of onset and increased symptoms of FA.
Most people with FA have two FXN genes with over 100 repeats. But FA can also be caused by other types of changes in the FXN gene. In these cases, the correct letter of the DNA sequence is replaced by a different letter or letters are deleted from the gene. Four percent of people with FA have one FXN gene with over 100 GAA repeats and one FXN gene with another type of mutation (point mutations, insertions, deletions, and others).
There is much known about the genetic cause of FA. Understanding FA at the genetic and cellular level (specific genetic mutations, the frataxin protein, and the mutation’s impact on mitochondria) allows scientists to develop treatments that address the disease from different approaches.
Currently, there are several treatment candidates on the Drug Development Pipeline being investigated that target the FXN gene or the frataxin protein. The first treatment approved for FA, SKYCLARYS™, more broadly improves mitochondrial health despite low levels of frataxin. FARA believes a cocktail approach — a combination of two or more therapies to address the multiple symptoms of FA — will be needed to cure FA.
Visit the Managing FA page to learn about ways to manage symptoms of FA with medications, physical therapy, and other medical interventions.
