Friedreich Ataxia

Excerpt

Friedreich ataxia (FA) is the most common hereditary ataxia accounting for approximately 50% of all ataxia cases. It was first reported in 1863 by the German physician Nikolaus Friedreich. The disease causes neurodegeneration and manifests as a combination of difficulty in ambulation, muscle weakness, loss of sensation and proprioception, and impaired speech. It has an autosomal recessive inheritance pattern, and symptom onset is usually in childhood. Unfortunately, symptoms worsen as time progresses, so most people affected by this disease end up requiring mobility aids such as wheelchairs, lose their vision and hearing, and develop other medical complications such as diabetes mellitus and scoliosis.

The most common cause of death in patients with FA is hypertrophic cardiomyopathy. Patients with FA have an abnormal amount of trinucleotide repeats on the frataxin (FXN) gene on chromosome 9. The frataxin gene is responsible for producing frataxin, a protein that helps form enzymes needed for mitochondrial adenosine triphosphate (ATP) production and management of iron stores. In FA, the pathological trinucleotide repeats result in gene silencing and a decrease in frataxin. Highly active cells depending on ATP production, such as neurons, cardiomyocytes, and pancreatic beta cells, are adversely affected.