Friedreich's ataxia is an autosomal recessive disorder that is the most common cause of hereditary ataxia, accounting for up to 50% of all cases. It is most commonly caused by a loss of function mutation in the frataxin (FXN) gene, located on chromosome 9q13. Frataxin is a mitochondrial protein involved in iron regulation, among other functions, and it has been found to be in particularly high levels in the tissues affected in Friedrich's ataxia, such as the brain, heart and pancreas. A longstanding hypothesis is that Friedrich's ataxia occurs as a result of excess iron accumulation, which leads to increased oxidative stress that causes cellular damage.
The onset of clinical manifestations is typically seen between ages 5 to 15, but cases have been reported to range from 2 to over 70 years of age. Neurologically, patients almost always present in adolescence with close to 100% having a limb ataxia that typically progresses to all 4 limbs. Deep tendon reflexes are lost in 90% of cases, motor weakness involving the feet and legs is seen in up to 88% of the time, and sensory loss in distal limbs is found in up to 92% of patients. Cerebellar dysarthria, dysphagia, vision loss, hearing loss, bladder dysfunction, and eye movement abnormalities are also seen, among others. Hypertrophic cardiomyopathy is commonly seen in Friedreich's ataxia, with the main clinical manifestations being arrhythmia and heart failure. Diabetes mellitus or impaired glucose tolerance is estimated in 8 to 32 percent of patients, and kyphoscoliosis affects 60% to 80% of all patients. However, it should be noted that up to one quarter of patients may present atypically, with either a late onset over 25 years of age, slower progression, and absence of cardiomyopathy, retained leg reflexes, as well as leg spasticity with little or no gait and limb ataxia.
On MRI, patients usually have a normal scan, but may show atrophy of the superior vermis, inferior cerebellar hemispheres, spinal cord, and occasionally the brainstem. DWI/DTI has been used to study this order, and some findings include increased diffusivity in the cerebellum and decreased fractional anisotropy in the superior cerebral peduncles. DWI has also been shown to be a good imaging modality to quantify the extent of neurodegeneration in Friedreich's ataxia, that appears more extended than previously reported, showing microstructural involvement in the optic radiations and cerebral peduncles.
References
1. Rizzo, G. , Tonon, C. , Valentino, M. L., Manners, D. , Fortuna, F. , Gellera, C. , Pini, A. , Ghezzo, A. , Baruzzi, A. , Testa, C. , Malucelli, E. , Barbiroli, B. , Carelli, V. and Lodi, R. (2011), Brain diffusion‐weighted imaging in Friedreich's ataxia. Mov. Disord., 26: 705-712.