Friedreich’s Ataxia

Friedreich’s ataxia is a rare inherited disorder that progressively damages the nervous system, affecting movement, balance, and coordination. While symptoms typically begin in childhood or adolescence, the disease’s progression varies greatly from person to person, and advances in care and treatment continue to improve outcomes for those living with this condition.

Table of contents

• What is Friedreich’s ataxia?
• Symptoms and signs
• Causes and genetic factors
• Diagnosis
• Treatment and management
• Disease progression and outlook
• Living with Friedreich’s ataxia

What is Friedreich’s ataxia?

Friedreich’s ataxia, often shortened to FA or FRDA, is a rare inherited disorder that causes progressive damage to the nervous system^[1]. The condition primarily affects the spinal cord (the main pathway for signals between the brain and body), peripheral nerves (nerves that connect the spinal cord to muscles and sensory organs), and the cerebellum (the part of the brain that coordinates balance and movement)^[2].

In Friedreich’s ataxia, nerve fibers in the spinal cord and peripheral nerves break down and become thinner^[1]. Some nerve cells also lose part of their protective covering called the myelin sheath, which normally helps nerve signals travel quickly and efficiently^[2]. This damage disrupts the flow of information between the brain and body, leading to the movement and coordination problems characteristic of the disease.

Although rare, Friedreich’s ataxia is the most common form of inherited ataxia (loss of coordinated movement) in the United States, affecting approximately 1 in 50,000 people^[3]. Worldwide, the condition affects about 1 in 40,000 people, with the highest rates among those of Western European descent^[2]. The condition is named after German physician Nikolaus Friedreich, who first described it in the 1860s^[2].

• Spinal cord
• Peripheral nerves
• Cerebellum
• Heart

Symptoms and signs

Symptoms of Friedreich’s ataxia typically begin between the ages of 5 and 15, although they can sometimes appear as early as age 2 or as late as age 50^[3]. When symptoms develop before age 25, the condition is considered typical FA. Late-onset Friedreich’s ataxia (LOFA) refers to cases where symptoms start after age 25, while very late-onset Friedreich’s ataxia (VLOFA) describes cases beginning after age 40. These late-onset forms usually progress more slowly than typical FA^[3].

The first signs of Friedreich’s ataxia are usually difficulty standing, walking, and problems with balance, known as gait ataxia^[3]. A child with FA might walk clumsily or appear unsteady, as if intoxicated^[20]. These initial balance and coordination issues typically worsen over time, and new symptoms may develop as the disease progresses^[1].

Neurological symptoms commonly include awkward and unsteady movements with impaired muscle coordination that worsens over time^[1]. People with FA experience loss of sensation in the arms and legs, which may spread to other parts of the body^[1]. Normal reflexes are lost, especially in the knees and ankles, and muscle tone may increase, a condition called spasticity^[1]. Many people also lose their ability to sense where their body parts are positioned, known as loss of proprioception^[3].

Speech and swallowing difficulties often develop as the condition progresses. Speech may become slow and slurred, a condition called dysarthria^[1]. Some people find it harder to swallow over time, which can affect eating and nutrition^[4]. Hearing and vision loss can also occur, though these symptoms may not be present at the time of diagnosis^[4].

About 70% of people with Friedreich’s ataxia develop scoliosis, which is a sideways curvature of the spine^[4]. Foot deformities such as high arches and inward turning are also common^[3]. Fatigue, or extreme exhaustion that affects everyday activities, impacts most people with FA^[4].

Heart problems are among the most serious complications of Friedreich’s ataxia. Many people develop cardiomyopathy, which is abnormal thickening of the heart muscle that can lead to heart failure or irregular heart rhythms^[1]. These heart conditions may not cause symptoms initially but can be detected through cardiac tests^[4]. Heart disease is the main cause of death in people with FA^[4].

About 3 out of 10 people with Friedreich’s ataxia develop diabetes^[3]. This can present in childhood or adulthood and requires regular screening since it can be managed with standard treatment approaches^[4].

Causes and genetic factors

Friedreich’s ataxia is caused by a change, or mutation, in a gene called FXN^[1]. This gene carries the genetic code for producing a protein called frataxin, which is necessary for the proper function of mitochondria, the energy-producing parts of cells^[1].

In Friedreich’s ataxia, an abnormal pattern in the DNA sequence appears hundreds or more times. This pattern, called a GAA triplet repeat, greatly disrupts the normal production of frataxin^[1]. Research suggests that without the expected level of frataxin, certain cells in the body, especially those in the peripheral nerves, spinal cord, brain, and heart muscle, produce energy less effectively^[1]. This leads to a buildup of toxic byproducts called oxidative stress, which damages cells and causes symptoms^[3].

The frataxin deficiency disrupts cellular energy production and leads to problems with iron-sulfur cluster biogenesis, a process essential for mitochondrial function^[2]. Although scientists don’t fully understand frataxin’s complete role, it helps mitochondria do their job of providing energy to cells^[3].

Friedreich’s ataxia is inherited in an autosomal recessive pattern^[2]. This means a person develops the condition when they inherit two changed copies of the FXN gene, one from each biological parent^[3]. The biological parents of someone with an autosomal recessive condition each carry one copy of the changed gene, but they typically don’t show signs or symptoms of the condition themselves^[3]. Because this is a genetic condition, it cannot be prevented^[3].

Diagnosis

Friedreich’s ataxia is a genetic disease, which means genetic testing is the gold standard for diagnosis^[4]. The genetic test examines the FXN gene, which is the causative gene in FA. However, reaching a definite diagnosis often takes time and involves several steps^[20].

The first step in diagnosing FA is often a blood test^[20]. Many people with Friedreich’s ataxia have a severe lack of frataxin, the protein produced by the FXN gene. Healthcare providers also evaluate clinical symptoms, particularly problems with balance and coordination, loss of reflexes, and abnormal coordination in the legs^[7].

Several diagnostic tests may be performed to rule out other conditions and assess the extent of nerve damage. These can include nerve conduction velocity (NCV) and electromyography (EMG) tests, which measure how well nerves and muscles are functioning^[20]. An MRI scan may be used to look for changes in the cerebellum or to rule out other causes of ataxia^[20]. X-rays might reveal scoliosis or other skeletal changes^[20].

Genetic testing provides the only way to reach a definite diagnosis of Friedreich’s ataxia^[20]. This test looks for the characteristic GAA triplet repeat expansion in the FXN gene. Getting a diagnosis is important because it helps doctors determine the best treatment and allows for proper monitoring of the condition^[20].

Treatment and management

While there is no cure for Friedreich’s ataxia, treatment focuses on managing symptoms and slowing disease progression^[2]. In 2023, the U.S. Food and Drug Administration approved omaveloxolone (brand name Skyclarys) as the first treatment specifically for Friedreich’s ataxia in people aged 16 years and older^[10].

Omaveloxolone works by reducing oxidative stress and inflammation in neurons, which helps improve motor function in some patients^[2]. It is a once-daily oral pill meant to improve neurological function and slow the progression of the disease^[12]. In clinical trials, patients taking omaveloxolone showed statistically significant improvements in their ability to move and coordinate compared to those taking placebo, and this benefit persisted over time^[11].

Managing Friedreich’s ataxia requires a team approach involving multiple healthcare specialists^[14]. Neurologists assess and manage symptoms related to ataxia, pain, spasticity, and muscle function. Cardiologists monitor the heart for signs of cardiomyopathy and abnormal heart rhythms, and treat cardiac symptoms. Since heart disease is a leading complication, standard treatments for heart failure and irregular heartbeats are administered as needed^[1].

Physical therapy, occupational therapy, and speech therapy play important roles in managing FA^[7]. Physical and occupational therapists help people build strength, maintain coordination as long as possible, and learn how to modify daily tasks^[14]. Exercising regularly, especially exercises that help with balance, coordination, and core stability, can help prevent symptoms from getting worse^[16]. Speech therapists can help manage symptoms of slurred speech and difficulty swallowing^[14].

Many assistive devices and tools are available to improve well-being and maintain independence. These range from walking aids and wheelchairs to hearing aids and other adaptive equipment^[16]. Endocrinologists can help manage diabetes, which affects about 30% of people with FA, using standard diabetes treatments^[3]. Orthopedic surgeons may be needed to treat scoliosis, which can progress in some individuals and require corrective surgery^[4].

Regular monitoring is essential. People with FA should see their healthcare providers regularly, typically every six months or so^[15]. Healthcare teams will want to monitor changes in mobility, balance, speech, swallowing, weight, sleep habits, and mood, as well as screen for cardiac problems and diabetes^[15].

Disease progression and outlook

The progression of Friedreich’s ataxia varies greatly from person to person^[1]. Generally, within 10 to 20 years after the appearance of the first symptoms, individuals with FA may need to use a wheelchair^[1]. In later stages of the disorder, people may become completely incapacitated^[1].

Friedreich’s ataxia is life-shortening, and heart disease is the most common cause of death^[1]. However, the outlook is not the same for everyone. Some people with less severe FA live into their sixties or older^[1]. The average life expectancy for those with less severe Friedreich’s ataxia is 60 years and older^[16].

Late-onset and very late-onset forms of Friedreich’s ataxia typically progress more slowly than typical FA that begins in childhood^[3]. Advances in care and treatment have improved outcomes for many individuals with Friedreich’s ataxia^[2]. The approval of omaveloxolone represents a significant milestone that has created excitement for both those living with FA and their caregivers^[9].

Living with Friedreich’s ataxia

Living with Friedreich’s ataxia presents challenges, but with the right support and resources, people can maintain quality of life and engage in meaningful activities^[15]. Creating a daily routine helps conserve energy and reduces stress, making it easier to maintain healthy habits like eating a proper diet and getting plenty of exercise^[15].

Being proactive about health is essential. This means seeing providers regularly, anticipating healthcare team questions, asking questions of your own, and keeping a symptom diary to spot trends and anticipate challenges before they arise^[15]. Advocating for yourself early and often, even when it means admitting that activities are becoming harder to manage, helps healthcare providers offer timely support and recommend helpful solutions^[15].

Mental health is an important aspect of living with a degenerative condition. Getting diagnosed with Friedreich’s ataxia can be challenging, and learning resilience and coping skills can help people get through difficult days and fully enjoy good ones^[15]. Talking about the condition with friends, family, or a therapist can provide valuable support^[16].

Connecting with others in the FA community can be beneficial. Many organizations offer support groups, educational events, and resources specifically for people with Friedreich’s ataxia and their families^[4]. These connections can provide practical advice, emotional support, and a sense of community with others who understand the challenges of living with FA.

For caregivers, knowing when to ask for help is one of the most important skills. Friedreich’s ataxia changes over time, and every person’s needs change as well^[19]. Keeping lines of communication open, knowing available resources, and staying adaptable are key to providing the best support. Working with a social worker can help identify additional support services as needs change^[19].