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.
The disease is progressive, with increasing staggering or stumbling gait and frequent falling. By the third decade, affected people lose the ability to stand or walk without assistance and require a wheelchair for mobility. Early-onset cases
Non-neurological symptoms such as scoliosis, pes cavus, cardiomyopathy and diabetes are more frequent amongst the early-onset cases. Genetics
FRDA is an autosomal-recessive disorder that affects a gene (FXN) on chromosome 9, which produces an important protein called frataxin.In 96% of cases, the mutant FXN gene has 90–1,300 GAA trinucleotide repeat expansions in intron 1 of both alleles. This expansion causes epigenetic changes and formation of heterochromatin near the repeat. The length of the shorter GAA repeat is correlated with the age of onset and disease severity. The formation of heterochromatin results in reduced transcription of the gene and low levels of frataxin. People with FDRA might have 5-35% of the frataxin protein compared to healthy individuals. Heterozygous carriers of the mutant FXN gene have 50% lower frataxin levels, but this decrease is not enough to cause symptoms.In about 4% of cases, the disease is caused by a (missense, nonsense, or intronic) point mutation, with an expansion in one allele and a point mutation in the other. A missense point mutation can have milder symptoms. Depending on the point mutation, cells can produce no frataxin, nonfunctional frataxin, or frataxin that is not properly localized to the mitochondria. Pathophysiology
FRDA affects the nervous system, heart, pancreas, and other systems.Degeneration of nerve tissue in the spinal cord causes ataxia.