Friedreich’s ataxia is a rare inherited disease that progressively damages the nervous system and the heart. It affects roughly 2 to 4 people per 100,000 worldwide, making it the most common inherited ataxia. Symptoms usually appear between ages 5 and 15, starting with difficulty walking and poor coordination, then gradually affecting other body systems over the following years and decades.
What Causes Friedreich’s Ataxia
The disease traces back to a single gene called FXN, which carries instructions for making a protein called frataxin. In healthy people, a short sequence of DNA (three letters: GAA) repeats a modest number of times inside this gene. In people with Friedreich’s ataxia, that sequence repeats far too many times, expanding beyond a threshold of about 60 repeats. Most affected individuals have hundreds of repeats on both copies of the gene.
This overexpansion causes the DNA in that region to fold into unusual structures that essentially lock the gene shut. The cell treats the area like inactive, silent DNA and stops reading it properly. The result: cells produce only about 10 to 30% of the normal amount of frataxin protein. Longer repeat expansions lead to less frataxin, earlier symptom onset, and more severe disease.
Frataxin works inside mitochondria, the structures that generate energy in every cell. It helps build tiny iron-containing components that are critical for moving electrons through the energy production chain. Without enough frataxin, mitochondria can’t produce energy efficiently and become vulnerable to damage from reactive oxygen molecules. This energy shortfall hits hardest in the cells that need the most power: nerve cells and heart muscle cells.
Because both copies of the FXN gene must carry the expansion for the disease to develop, Friedreich’s ataxia follows an autosomal recessive inheritance pattern. Both parents must be carriers. Carrier rates are estimated at 1 in 60 to 1 in 100 people, and carriers themselves have no symptoms.
Early Symptoms and How They Progress
The first sign is almost always difficulty with walking and balance. Children or teenagers notice they stumble more, have trouble with turns, or feel unsteady on uneven ground. This unsteadiness, called ataxia, worsens over time and eventually affects the arms and trunk as well.
Alongside coordination problems, sensory loss develops in the arms and legs. The nerves that carry position and vibration information to the brain deteriorate, so the body loses its internal sense of where its limbs are in space. Reflexes at the knees and ankles typically disappear early. Speech gradually becomes slower and harder to understand as the muscles controlling articulation lose coordination. Fatigue is common and often underestimated.
Other neurological changes can include increased muscle stiffness, difficulty swallowing, and, in some cases, hearing or vision loss. Scoliosis (a sideways curvature of the spine) and high-arched feet are frequent skeletal findings. Most people with the classic childhood-onset form need a wheelchair within 10 to 15 years of their first symptoms, though the timeline varies considerably based on repeat length and individual factors.
Heart Disease and Diabetes
The heart is the organ most dangerously affected outside the nervous system. Between two-thirds and nearly all people with Friedreich’s ataxia develop some form of cardiomyopathy, a thickening and weakening of the heart muscle. The most common pattern is concentric left ventricular hypertrophy, where the walls of the heart’s main pumping chamber grow abnormally thick. Studies have detected this thickening in 45 to 68% of affected children at the time of evaluation.
Cardiac dysfunction is the leading cause of death, responsible for roughly 59% of deaths in people with Friedreich’s ataxia. Congestive heart failure and irregular heart rhythms are the primary cardiac events. Heart-related deaths tend to occur earlier in the disease course than non-cardiac deaths.
Diabetes is the other major systemic complication. About 18% of affected individuals develop overt diabetes, while impaired glucose tolerance (a pre-diabetic state) is present in up to 39%. The combination of mitochondrial dysfunction and possible damage to insulin-producing cells in the pancreas likely drives this risk.
How It’s Diagnosed
Diagnosis starts with a clinical evaluation. A neurologist will look for the characteristic combination of progressive ataxia beginning in childhood, absent reflexes in the lower limbs, and sensory loss, often alongside scoliosis or foot deformities. A genetic test confirms the diagnosis by measuring the number of GAA repeats in the FXN gene. Finding expanded repeats on both copies of the gene is the definitive confirmation. In rare cases, a person may have an expansion on one copy and a different type of mutation on the other.
Because late-onset forms exist (symptoms appearing after age 25), Friedreich’s ataxia can sometimes be overlooked in adults. Genetic testing is recommended whenever an unexplained progressive ataxia develops, regardless of the patient’s age.
The First Approved Treatment
For decades, no drug was approved specifically for Friedreich’s ataxia. That changed in 2023, when omaveloxolone (brand name Skyclarys) became the first FDA-approved therapy for the condition in adults and adolescents aged 16 and older. It’s taken as three 50 mg capsules once daily.
Omaveloxolone works by activating a cellular defense pathway that is suppressed when frataxin levels are low. This pathway helps cells manage oxidative stress and restore some mitochondrial function. In the pivotal clinical trial, patients taking omaveloxolone showed a 2.4-point improvement on a standardized ataxia rating scale compared to those on placebo, a modest but statistically significant difference that reflected better neurological function. The drug does not replace the missing frataxin protein or fix the underlying gene, but it addresses some of the downstream damage.
Rehabilitation and Daily Management
Physical therapy remains a cornerstone of care throughout the disease. Programs typically focus on maintaining balance, trunk stability, and upper-limb coordination for as long as possible. Occupational therapy helps people adapt daily tasks like dressing, eating, and writing as fine motor control changes. Mobility aids, from ankle braces to walkers to wheelchairs, are introduced as needed to keep people safe and independent.
Speech therapy addresses both the slurred speech (dysarthria) that develops over time and swallowing difficulties that can lead to choking or aspiration. Swallowing evaluations are a routine part of multidisciplinary care. Scoliosis may require bracing or, in more severe cases, surgical correction. Regular cardiac monitoring with echocardiograms and electrocardiograms is essential to catch heart changes early, and blood glucose screening helps identify diabetes before it causes additional complications.
Gene Therapy on the Horizon
Because Friedreich’s ataxia stems from a single gene defect, it is a strong candidate for gene therapy. The first human gene therapy trial for the condition began in 2022 at Weill Cornell Medical College, targeting the heart complications specifically. A follow-up phase 1/2 trial is testing different doses of an intravenous gene therapy designed to deliver a working copy of the FXN gene to heart cells.
Gene editing approaches using tools like CRISPR are also under investigation in laboratory studies. The strategy here is different: rather than adding a new gene, researchers aim to remove the expanded GAA repeat from the existing gene, which has been shown to restore frataxin production in cell models. Several companies have preclinical programs exploring both gene replacement and gene editing for Friedreich’s ataxia, though these are still years from reaching patients.
Life Expectancy and Outlook
Life expectancy for people with Friedreich’s ataxia is shortened, primarily due to heart disease. Many studies place the median age of death in the mid-30s to early 40s for those with classic childhood-onset disease, though individuals with later onset or shorter repeat expansions can live significantly longer. The wide range in repeat lengths, from a few hundred to over a thousand, translates into a wide range of disease severity and outcomes.
Cardiac care has improved meaningfully over the past two decades, and the approval of omaveloxolone adds a new tool for managing neurological progression. With gene therapy trials actively enrolling and multiple other approaches in development, the treatment landscape for Friedreich’s ataxia is shifting faster than at any point in the disease’s history.