The sensory neurons essential for directing muscle movement of the arms and legs through connections with the cerebellum are particularly affected. The disease primarily affects the spinal cord and peripheral nerves. The spinal cord becomes thinner and nerve cells lose some myelin sheath. The diameter of the spinal cord is smaller than that of unaffected individuals mainly due to smaller dorsal root ganglia. The motor neurons of the spinal cord are affected to a lesser extent than sensory neurons. In peripheral nerves, a loss of large myelinated sensory fibers occurs.Structures in the brain are also affected by FRDA, notably the dentate nucleus of the cerebellum. The heart often develops some fibrosis, and over time, develops left-ventricle hypertrophy and dilatation of the left ventricle. Frataxin
The exact role of frataxin remains unclear. Frataxin assists iron-sulfur protein synthesis in the electron transport chain to generate adenosine triphosphate, the energy molecule necessary to carry out metabolic functions in cells. It also regulates iron transfer in the mitochondria by providing a proper amount of reactive oxygen species (ROS) to maintain normal processes. One result of frataxin deficiency is mitochondrial iron overload, which damages many proteins due to effects on cellular metabolism.Without frataxin, the energy in the mitochondria falls, and excess iron creates extra ROS, leading to further cell damage. Low frataxin levels lead to insufficient biosynthesis of iron–sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase and iron dysmetabolism of the entire cell.
The symptoms are broad, but consistently involve gait and limb ataxia, dysarthria and loss of lower limb reflexes. Classical symptoms
There is some variability in symptom frequency, onset and progression. All individuals with FRDA develop neurological symptoms, including dysarthria and loss of lower limb reflexes, and more than 90% present with ataxia. Cardiac issues are very common with early onset FRDA . Most individuals develop heart problems such as enlargement of the heart, symmetrical hypertrophy, heart murmurs, atrial fibrillation, tachycardia, hypertrophic cardiomyopathy, and conduction defects. Scoliosis is present in about 60%. 7% of people with FRDA also have diabetes and having diabetes has an adverse impact on people with FA, especially those that show symptoms when young. Other symptoms
People who have been living with FRDA for a long time may develop other complications. 36.8% experience decreased visual acuity, which may be progressive and could lead to functional blindness. Hearing loss is present in about 10.9% of cases. Some patients report bladder and bowel symptoms. Advanced stages of disease are associated with supraventricular tachyarrhythmias, most commonly atrial fibrillation.Other later stage symptoms can include, cerebellar effects such as nystagmus, fast saccadic eye movements, dysmetria and loss of coordination (truncal ataxia, and stomping gait). Symptoms can involve the dorsal column such as the loss of vibratory sensation and proprioceptive sensation.The progressive loss of coordination and muscle strength leads to the full-time use of a wheelchair. Most young people diagnosed with FRDA require mobility aids such as a cane, walker, or wheelchair by early 20s.