26th June 2023

Friedreich’s Ataxia

Friedreich’s ataxia is an autosomal recessive neurodegenerative disease caused by a mutation (typically a GAA trinucleotide repeat expansion in 98% of cases) in the FXN gene on chromosome 9, resulting in reduced production of frataxin. It is the most common of the inherited ataxias with an incidence of 1:150,000 and results in both spinal cord axonopathy and demyelination, with widespread alteration in cellular phospholipid metabolism, affecting mainly the dorsal root ganglia, posterior columns of the spinal cord, corticospinal tracts, dorsal spinocerebellar tracts and also the heart. Progressive destruction of the dentate nucleus with atrophy of Betz cells also occurs intracranially.

Clinical features are loss of vibration sense and proprioception with progressive gait and limb ataxia, absent lower limb reflexes and extensor plantar responses with limb weakness and atrophy. Dysarthria and dysphagia can also develop, and many patients will suffer from cardiomyopathy, kyphoscoliosis, and foot deformities such as pes cavus.

Investigations include MRI imaging, EMG, nerve conduction studies, echocardiogram, and genetic testing. Nerve conduction studies will characteristically show absent sensory nerve action potentials and absent spinal somatosensory evoked potentials, with motor nerve conduction velocities reduced to a lesser extent than sensory nerve action potentials.

Management is supportive, with a focus on rehabilitation and orthoses, with management of any complications, e.g. heart failure. Prognosis is variable and dependent on age and the specific genetic mutation in the FXN gene, with patients surviving into their 30s and some living into their 60s.