Friedreich’s ataxia
Friedreich’s ataxia (FA) is a hereditary neurological degenerative disease characterized by spinocerebellar degeneration (a disease of the tracts going from the cerebellum to the spinal cord). It starts most often during childhood, usually between the ages of 5 and 18 (though younger cases and some in adults can be found) by troubles walking and brings a progressive handicap associated with motor troubles and cardiac disease.
The ataxia causes an inability to coordinate voluntary muscle movements (ataxia) attributable to the premature death of the nervous cells which control balance and coordination. With these troubles are associated the possibility of a thickening of the cardiac muscle (cardiomyopathy) due to the reduced production of a protein, frataxin.
This decrease in frataxin brings an excessive accumulation of iron in the cells, which results in a poor functioning of the mitochondria particularly on the level of the nervous system and the heart. Mitochondria are the structures which generate energy on the cellular level. This poor functioning of the mitochondria is also manifested by an excessive increase of certain products in the blood such as malondialdehyde. (Dr. Michel Vanasse, neurologist, Sainte-Justine Hospital, Montreal).
FA is a recessive autosomal disease; it affects both sexes and both parents must transmit the gene to have a child affected by the disease. The disease, although it is hereditary, is not always present in each generation. A carrier of the gene is asymptomatic and there is a 25% chance that the child will have FA.
FA affects the upper and the lower limbs, the muscles of the trunk, the neck and the head. It causes a loss of positioning sense mainly in the lower limbs which makes balance difficult (coordination and precision). At the beginning, there are troubles walking and balancing, little by little, walking becomes unstable with an increasing distance between the feet, inequality of steps, excessive spacing of the lower and upper limbs. The person begins to need help to move around.
As the disease progresses, other symptoms can manifest themselves such as the loss of certain reflexes, fatigue, problems of elocution and articulation (difficulty speaking, with an explosive and slow voice, irregularity in the tone and the intensity of the voice).
Swallowing is sometimes difficult, and, in many cases, there will be a loss of coordination of the ocular muscles (irregular movements of the eyes), and a loss of visual and auditory acuity (deterioration of the visual and auditory nerves). A deformation of the spinal column is also present in a great number of affected people and hollow feet as well (the top of the foot will bulge and the bottom in the center will be hollow).
Because of the evolution of the disease, usually between 8 to 10 years following the first sign of symptoms, the affected person will have to use a wheelchair in order to palliate his or her inability to walk.
Cardiac problems (cardiomyopathy, i.e., the heart muscle is thicker than normal and causes anomalies of the rhythm of the cardiac pulse) happens in about two thirds of the cases of FA. Diabetes can sometimes also be present, about 30%.
The evolution is faster at the beginning and the affected people will see themselves confined to a wheelchair. The evolution and the symptoms can be different from one person to another even if these people belong to the same family.
A blood sample is enough to know if an individual is healthy, a carrier, or has the disease.
Neurological follow-up can measure evolution of the disease in order to better guide the patient to the clinical and technical services required. Cardiac and diabetes follow-up may likewise be necessary.
Cardiac problem can give the seriousness of the disease and the final diagnosis.
Rehabilitation allows one to limit functional losses and avoid deformations, therefore complications. Occupational therapy, physiotherapy, and speech therapy can be done in order to limit functional losses and to prevent certain complications. Insulin and certain agents are used to treat diabetes.
Active management of spasticity can help prevent permanent contractures and treatment of scoliosis is also done to prevent cardiopulmonary complications.
For the moment, no cure exists. However, many clinical trials are ongoing.
Articles:
Friedreich ataxia- pathogenesis and implications for therapies
Sources:
https://www.ncbi.nlm.nih.gov/books/NBK1281/
https://ataxia.org/wp-content/uploads/2019/04/Friedreich-Ataxia.pdf
FARA treatment pipeline:
https://www.curefa.org/pipeline
There are some ongoing clinical trials as well.
https://www.clinicaltrials.gov
https://www.curefa.org/trial (patient registry)