Friedreich ataxia is the most common hereditary progressive ataxia.

Epidemiology

Thought to have an estimated prevalence of ~1:50,000. There is no recognized gender predilection.

Clinical presentation

There are a wide variety of potential clinical manifestations ¹¹. It typically presents in childhood to adolescence ¹¹. Those with a higher number of trinucleotide repeats (>500) are thought to present at an earlier age and with a more severe clinical phenotype ¹.

• neurological

  • cerebellar and spinocerebellar tract involvement: four-limb ataxia, gait ataxia, cerebellar dysarthria

  • lateral corticospinal tract involvement: upper motor neuron pattern weakness

  • dorsal columns involvement: vibration and proprioceptive loss

  • dorsal root ganglia involvement: areflexia

• musculoskeletal

  • kyphoscoliosis

  • pes cavus

  • talipes equinovarus

• hypertrophic cardiomyopathy

• diabetes mellitus

Pathology

Genetics

The condition results from an expansion of an unstable GAA trinucleotide repeat in the FXN gene located on chromosome 9q ^1,6,11. This gene encodes for frataxin, a protein that has multiple important roles in relation to iron in various tissues of the body, but most prominently the brain, heart and pancreas ¹¹. Friedreich ataxia carries an autosomal recessive inheritance ¹.

Microscopic appearance

In the posterior and lateral columns of the spinal cord, there is a loss of myelinated fibers and gliosis.

Radiographic features

MRI

In the brain and spinal cord:

• may show thinning (reduction in AP diameter) of the cervical cord ²

• cerebral and cerebellar atrophy may also be evident ⁵

• DWI with mean diffusivity maps may be a suitable non-invasive technique to quantify the extent of neurodegeneration in Friedreich ataxia, showing a microstructural involvement of structures such as optic radiation and middle cerebellar peduncles ¹⁰

  • this is largely a research tool

Treatment and prognosis

Management is generally supportive, including screening of complications (e.g. hypertrophic cardiomyopathy, dysphagia). Omaveloxolone, an Nrf2 activator, may have benefit in improving neurological symptoms ¹².

History and etymology

It is named after Nikolaus Friedreich (1825-1882), a German physician.

Differential diagnosis

• spinocerebellar ataxia

• dentatorubral-pallidoluysian atrophy

• ataxia-telangiectasia​