Signs and Symptoms of Friedreich's ataxia

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.

Boy with ataxic gait.

Ataxia (balance difficulty)
Beating heart

Heart Conditions
Xray image of spine

Scoliosis (curvature of the spine)
image used for diabetes - young girl

Diabetes
female with fatigue - glasses in hand sitting in chair

Fatigue
Dysarthria word illustration

Dysarthria (slurred speech)
Image for vision - two circles for glasses

Vision Impairment
image of ear

Hearing Impairment
medical professional with tablet and stethoscope

Other Signs and Symptoms

More on Signs and Symptoms

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. The progression of ataxia eventually makes walking difficult, and individuals with FA use a wide range of mobility devices including walkers, rollators, manual wheelchairs, mobility scooters, and power wheelchairs. On average, those with childhood onset FA require full-time use of a wheelchair for mobility about ten years after symptoms begin, while those who have later onset of symptoms retain the ability to walk for longer.

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.

When FA Symptoms First Appear

Age of Onset

Friedreich’s ataxia can affect people in different ways. The age when symptoms first appear, often called age of onset, is associated with differences in how FA presents and progresses. Exact age of onset can be difficult to pinpoint, but it is generally defined as the age at which symptoms become noticeable enough to seek medical advice. Age of onset is related to the underlying genetics of FA. People with FA have expanded GAA repeats in both of their FXN genes. The smallest number of repeats between both genes is linked to age of onset, with more repeats on the smallest gene associated with earlier age of onset. In general, earlier onset may be associated with a more rapid progression, while later onset may be associated with slower progression of neurological symptoms. Our current understanding of how age of onset relates to symptoms and progression comes from natural history research.

Some individuals and families find it helpful to connect with others who have a similar age of onset, as it can provide shared understanding and support. If you’d like to be connected to other families living with FA, please reach out to us at: info@curefa.org or call the FARA office at (484) 879-6160.

 

Different Ages of Onset

Researchers have determined four broad age of onset categories: early childhood, childhood, adolescent/early adult, and adult onset. The population studied through natural history research does not necessarily reflect the full diversity of the FA population, as all research has limitations and biases based on who chooses to participate. Age of onset categories are used in research to describe patterns seen across many people, but they can’t define or predict what any one person’s experience will be.

In the UNIFAI natural history study, 29% of participants have early childhood onset FA or symptoms that begin before the age of 8. Parents and caregivers may first notice changes in balance or coordination or an unusual amount of fatigue after physical activity. In this age group, it can sometimes be difficult to distinguish between neurological symptoms and the normal variability of acquiring motor skills and developmental milestones throughout early childhood. In other cases, a heart-related concern, such as the detection of a heart murmur or difficulty breathing when exercising or playing, may be the first sign of FA. Over time, individuals may experience changes in multiple parts of the body, including cardiomyopathy, scoliosis, diabetes, and vision and hearing loss. However, there is a wide range of experiences from child to child.  Care for children in early childhood often involves monitoring across multiple areas of health and adapting support over time.

39% of participants in the UNIFAI natural history study have childhood onset FA, or symptoms that begin between the ages of 8–14 years. Because this is the most common age of onset, researchers call this group “typical onset FA.” Early signs often develop gradually and may include changes in balance, coordination, or walking, sometimes recognized when a child has more difficulty with running or keeping up on the playground. Many children also experience fatigue and may need to rest after school or have trouble participating in multiple extracurricular activities. Over time, individuals may experience changes in multiple parts of the body, including cardiomyopathy, scoliosis, diabetes, and vision and hearing loss. However, even within this most common group, the timing and progression of symptoms can vary significantly from person to person. Care teams can help families understand what to watch for, how symptoms may change over time, and how to support their child as needs evolve.

In the UNIFAI natural history study, 21% of participants have adolescent/early adult onset, or symptoms that begin between the ages of 15–24 years. Researchers call this group “intermediate onset FA.” Individuals may first notice gradual changes in coordination, balance, walking, or endurance. Running, sports, or long walks can become more difficult. In some cases, evaluation for scoliosis may be what leads to an FA diagnosis. Individuals with adolescent/early adult onset of symptoms may experience a more gradual progression than those whose symptoms began earlier in life, including retaining the ability to walk for longer. Not every individual will have cardiomyopathy, diabetes, or other symptoms outside of the nervous system. Ongoing care and follow-up remain an important part of living with FA, helping individuals adapt to changes over time.

In the UNIFAI natural history study, 11% of  participants have adult onset FA or symptoms that begin after age 25. This is often called late onset FA, and some clinicians and researchers may refer to onset after age 40 as “very late onset FA.” Adults may notice gradual changes in balance, coordination, or walking. On average, progression tends to be slower than when FA begins earlier in life, and many people retain walking ability for longer after symptoms first appear. Individuals with adult-onset FA are less likely to experience cardiomyopathy, diabetes, and other non-neurological symptoms. The slower progression of symptoms and the lack of awareness of late onset FA among doctors and healthcare workers can contribute to delays in diagnosis. Doctors with expertise in FA can help individuals understand whether new or worsening symptoms are related to FA or are just part of the natural process of aging.

The age of onset categories above refer to when an individual’s symptoms begin, not when a positive genetic test is received. Some individuals learn they have FA before any symptoms appear, which is called presymptomatic diagnosis. This often happens when an individual is given a genetic test for FA after a sibling or other relative’s diagnosis. If you or your child has received a presymptomatic diagnosis, talk to your doctor about how to better understand when symptoms may begin to arise and what early symptoms might look like. The length of the smallest GAA triplet repeat expansion and the age of onset of the symptomatic sibling may help predict this, but it is not a perfect estimate.

Rarely, some individuals may receive a genetic diagnosis of FA through a broad genetic test (like exome or genome sequencing) that was done to search for a genetic cause for issues such as developmental delay or other neurobehavioral symptoms. In these cases, it’s important to understand whether the symptoms that prompted the genetic test are potentially related to FA or whether you or your child may develop symptoms of FA in the future. This type of result may mean that you or your child has two diseases: FA plus the disease causing the current symptoms. Talking with a genetics professional or an FA specialist can help you understand what the genetic testing results mean for you or your child.

Journey to an FA Diagnosis

On average, it takes about 4 years for someone to receive a diagnosis of FA. Diagnosis may take longer for those with adult or late onset FA. Reducing barriers to diagnosis is an important area of research and advocacy for FARA and other rare disease organizations.

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.

Each person with FA has a different journey that leads them to a genetic diagnosis. Click below to read more.

Visit Newly Diagnosed Page
Image displaying steps in FA diagnostic journey—experiencing symptoms, examined by specialist who suspects FA, and genetic testing establishes FA diagnosis.

Diagnostic FAQs

Most individuals or families 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 others, 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 family doctor or your child’s pediatrician. 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 or your child’s symptoms are and why they might be occurring. These tests can be as simple as the neurologist watching you or your child walk down the hallway or reach out to grab an object. The neurologist will also ask you for a history of symptoms and test your or your child’s reflexes. Some clues that might make the neurologist consider FA 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 such as nerve conduction testing or an MRI of the brain and spinal cord.

If your neurologist has a suspicion that FA is the cause for your or your child’s symptoms, they may give you or your child 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 or your child 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.

Depending on the lab, a blood or saliva sample will be taken to collect your or your child’s DNA. It will likely take a few weeks for the results of the test to come back.

A positive test result means that you or your child 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 additional genetic testing 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:

  • Charcot Marie Tooth disease or other causes of peripheral neuropathy
  • Other genetic causes of ataxia including:
    • Spinocerebellar ataxia
    • Ataxia with Vitamin E deficiency
    • Ataxia with oculomotor apraxia
  • Mitochondrial diseases
  • Idiopathic scoliosis
  • Other genetic causes of cardiomyopathy

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. However, if symptoms  continue to 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.

GENETICS OF FRIEDREICH'S ATAXIA

What causes FA?

Friedreich’s ataxia is caused by mutations in the FXN gene, which encodes the instructions to make a protein called frataxin.

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.

DNA genetics image
FRIEDREICH'S ATAXIA AND RECESSIVE INHERITANCE

How is FA inherited?

FA is inherited in a recessive pattern.

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.

FA occurs most commonly in people of European, Northern African, and West/Central/South Asian ancestry. In these populations, it’s estimated that about 1 in every 100, or 1%, of people are carriers. 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.

A diagram showing that two carrier parents have a 25% chance of having an unaffected child, a 50% chance of having a child who's a carrier, and a 25% chance of having an affected child.
TRIPLET REPEAT EXPANSION AND OTHER MUTATIONS

What genetic mutations are seen in FA?

Triplet Repeat Expansions

Most people with FA have the same type of mutation in 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 to over 66 repeats on both copies of the gene.

Usually individuals with FA have a different number of repeats on each gene. Age of symptom onset has been linked to the length of the shortest GAA repeat, with longer repeats associated with earlier age of onset. For example, someone who has 200 repeats on one gene and 1000 repeats on the other gene is more likely to have onset of symptoms in adulthood because their shortest gene has only 200 repeats. While knowing your or your child’s exact repeat lengths can be useful, the age at which symptoms onset is a better predictor of how FA symptoms will evolve and progress than the number of GAA repeats.

Point Mutations and Other Mutations

Most people with FA have two FXN genes with over 66 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 or added to the gene. Four percent of people with FA have one FXN gene with over 66 GAA repeats and one FXN gene with another type of mutation (point mutations, insertions, deletions, and others).

Genetic knowledge leads to genetic therapies

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.

Understanding Genetic Therapies for Friedreich’s Ataxia

Drug Development Pipeline

There are several treatment candidates on the Drug Development Pipeline being investigated that target the FXN gene or the frataxin protein. There is one treatment approved for people with FA 16 years of age and older, that more broadly improves mitochondrial health despite low levels of frataxin. FARA believes multiple therapeutic approaches will be needed to treat and cure FA.

Drug Development Pipeline Participate in Research
drug development pipeline

Current Treatments and Management for FA

Visit the Managing FA page to learn about ways to manage symptoms of FA with medications, physical therapy, and other medical interventions.

Approved Treatment Managing FA