Friedreich's Ataxia

What causes Friedreich's ataxia

Friedreich's ataxia is autosomal recessive: a child must inherit an altered FXN gene from each parent. Parents are usually healthy carriers. When both parents are carriers, each child has a 1 in 4 chance of being affected.

The usual mutation is an expanded GAA triplet repeat in the FXN gene. Normal genes have fewer than about 33 repeats; affected people usually have hundreds to over a thousand. The expansion lowers production of frataxin, a protein needed for mitochondria to make energy and handle iron. Nerve cells, heart muscle cells and insulin-producing cells are especially vulnerable. Longer repeats are linked to earlier onset and more severe disease.

It affects about 1 in 40,000 to 50,000 people of European, Middle Eastern, North African and South Asian descent.

Symptoms

Neurological

• unsteady, wide-based walking and frequent falls, usually the first sign
• clumsiness and poor hand coordination
• slurred speech (dysarthria) and later swallowing problems
• loss of reflexes in the legs
• loss of position and vibration sense, worse in the dark. See loss of vibration sense
• muscle weakness, especially in the legs
• abnormal eye movements, hearing loss and optic nerve damage in some

Skeletal

• scoliosis, in most people
• high-arched feet (pes cavus) and curled toes

Heart

• hypertrophic cardiomyopathy in most patients, which can lead to heart failure and arrhythmias. Heart disease is the most common cause of death.

Other

• diabetes in about 10% to 30%
• bladder urgency and fatigue

Most people need a wheelchair 10 to 20 years after symptoms begin, although late-onset forms progress more slowly.

Diagnosis

• Neurological exam: ataxia, absent leg reflexes, upgoing toes, sensory loss.
• Genetic testing: confirms GAA repeat expansions in both FXN genes. This is the definitive test.
• Nerve conduction studies: show sensory nerve damage.
• MRI: may show spinal cord thinning.
• Heart tests: ECG and echocardiogram at diagnosis and regularly afterward.
• Blood sugar and HbA1c.
• Vitamin E level to rule out ataxia with vitamin E deficiency, which looks similar and is treatable. See vitamin E deficiency.

Treatment

Disease-slowing medicine

Omaveloxolone was approved by the FDA in 2023 for adults and adolescents aged 16 and older. It activates protective cellular pathways and in trials slowed progression of neurological decline. It requires monitoring of liver enzymes and cholesterol.

Supportive care

• Physical therapy for balance, strength and mobility; walking aids and wheelchairs as needed
• Occupational therapy for daily activities and adaptive equipment
• Speech and swallowing therapy
• Heart care: regular monitoring, medicines for heart failure and arrhythmias, and sometimes implantable devices
• Diabetes management
• Scoliosis: bracing or spinal surgery
• Foot surgery for severe deformities
• Hearing and vision aids
• Mental health support for the person and family

Outlook

Friedreich's ataxia is progressive and shortens life expectancy, mainly due to heart disease, but the course varies widely. Many people live into their 30s and 40s or beyond, and those with late-onset disease often longer. New treatments and ongoing clinical trials, including gene therapies, offer hope.

Frequently asked questions

What are the first signs of Friedreich's ataxia?

The first sign is usually unsteady walking and frequent falls in a child or teenager, often with clumsiness. Other early signs include high-arched feet, scoliosis and loss of reflexes. Heart problems may be found before neurological symptoms in some people.

What is the life expectancy with Friedreich's ataxia?

It varies widely. Average life expectancy has historically been in the late 30s, mainly due to heart disease, but many people live much longer, especially with later onset or milder disease. Better heart care and new treatments are improving outcomes.

How is Friedreich's ataxia inherited?

It is autosomal recessive. A person must inherit an altered FXN gene from both parents. When both parents are carriers, each child has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting neither altered gene.

Is there a treatment for Friedreich's ataxia?

Yes. Omaveloxolone is approved for people aged 16 and older and can slow neurological decline. Physical therapy, heart monitoring and treatment, diabetes care and scoliosis management help with symptoms. Gene therapies are being studied in clinical trials.