Friedreich’s ataxia: symptoms, genetics and care in the UK

Ataxia means a loss of muscle coordination. The Brain Charity describes Friedreich’s ataxia as a condition that affects a person’s coordination, balance and speech, caused by a hereditary faulty gene that leads to degeneration of part of the brain called the cerebellum, or of the spinal cord. The NHS Genomics Education Programme (GeNotes) characterises it as progressive ataxia with loss of muscle coordination and strength, spasticity and increasing sensory dysfunction, particularly in the legs.

It is a multisystem condition. The same GeNotes page lists cardiac features as common and significant, endocrine features such as glucose intolerance and diabetes, curvature of the spine and foot deformities, visual and hearing problems and sleep-disordered breathing. This breadth is why teams from several specialities are involved.

GeNotes says the first symptoms are usually gait ataxia or general clumsiness, followed by weakness in the legs, loss of coordination in the arms and speech difficulty (dysarthria). Reflexes at the knees and ankles are often absent, and sensation of vibration and position in the legs is reduced. The Brain Charity’s list is similar and adds difficulty swallowing, scoliosis, diabetes, hypertrophic cardiomyopathy and loss of sensation in the hands and feet.

• Unsteadiness, clumsiness and frequent falls.

• Slurred, slow or unclear speech.

• Increasing leg weakness and stiffness (spasticity).

• Difficulty swallowing in some people.

• Curvature of the spine and foot deformities such as high arches.

• Eye movement problems, and in some people visual loss later in the course.

• Hearing loss in some people.

• Heart muscle thickening (cardiomyopathy) and rhythm problems.

• Glucose intolerance and diabetes.

• Low mood and anxiety, which GeNotes says are common.

Diagnosis usually follows referral to a neurologist after a GP notices progressive problems with balance or coordination in a young person. GeNotes lists tests that aid diagnosis and management: nerve conduction studies, MRI or CT which may show spinal and cerebellar thinning, ECG and echocardiogram, and glucose and HbA1c tests. It states that genomic testing provides a conclusive diagnosis.

The genetics are straightforward to describe. Friedreich’s ataxia is caused by changes in both copies of the FXN gene, which makes a protein called frataxin that is believed to be critical for the assembly of iron and sulphur used by many proteins, including those with roles in energy production. In 96% of affected individuals the cause is a GAA triplet repeat expansion in the first intron of the gene on both copies. GeNotes notes that the repeat size on the shorter copy is related to age of onset and to heart involvement, but that on its own it cannot predict the course for an individual.

Friedreich’s ataxia is autosomal recessive, meaning that the parents of most affected people are healthy carriers. GeNotes states that when both parents are carriers there is a 1 in 4 (25%) chance in each pregnancy of a child being affected, a 1 in 2 (50%) chance of the child being a healthy carrier and a 1 in 4 (25%) chance of the child being neither. It gives the carrier frequency as around 1 in 85 in populations with a high proportion of people of European or Indian ancestry.

Testing for the expansion in at-risk relatives and partners is available, as is prenatal testing if required. NHS clinical genetics services offer genetic counselling to explain the options, and this is usually arranged through a neurology or genetics clinic.

GeNotes says there is currently no cure, and that management is complex and should be delivered by a multidisciplinary team. It lists the following as part of symptomatic management and surveillance, all aimed at maintaining quality of life.

GeNotes says a single medicine, omaveloxolone, which activates the Nrf2 pathway, has been licensed in some countries for people over 16, and that it was undergoing NICE evaluation and was not yet licensed in the UK at the time the page was written. Licensing and NICE recommendations change, so ask your neurology team or Ataxia UK for the current position. A number of other potential treatments are in clinical trials.

GeNotes states that the average time from onset to wheelchair dependence is 10 to 20 years and that life expectancy varies with age of onset and the presence of heart muscle disease or diabetes, with a mean of around 35 to 40 years. These are averages from group data and individual courses vary, including milder, later-onset forms. Regular cardiac and diabetes checks are an important way to reduce avoidable complications.

The Brain Charity provides practical help and emotional support for people with Friedreich’s ataxia and their carers across the UK, and lists Ataxia UK as a source of support groups and a helpline. Ask your GP or consultant about social care, occupational therapy and benefits advice, and about psychological support, since depression and anxiety are common.