Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system resulting in symptoms ranging from gait disturbance and speech problems to heart disease.
Generally, ataxia is a symptom of coordination problems such as clumsy or awkward movements and unsteadiness and occurs in many different diseases and conditions. The ataxia of Friedreich's ataxia results fromthe degeneration of nerve tissue in the spinal cord, in particular sensory neurons essential (through connections with the cerebellum) for directing muscle movement of the arms and legs. The spinal cord becomes thinner and nerve cells lose some of their myelin sheath (the insular covering on some nerve cells that helps conduct nerve impulses).
Contents[hide] * 1 Eponym * 2 Prevalence * 3Genetics * 4 Relationship to muscular dystrophy * 5 Symptoms * 6 Signs * 7 Pathogenesis * 8 Treatment * 9 See also * 10 External links * 11 References |
The condition is named after the German physician Nicholaus Friedreich, who first described it in the 1860s.
Friedreich's ataxia is the most prevalent inherited ataxia, affecting about 1 in50,000 people in the United States. Males and females are affected equally. The estimated carrier prevalence is 1:110.
A 1984 Canadian study was able to trace 40 cases of classical Friedreich's disease from 14 French-Canadian kindreds previously thought to be unrelated to one common ancestral couple arriving in New France in 1634: Jean Guyon and Mathurine Robin.
Friedreich'sataxia has an autosomal recessive pattern of inheritance.
Friedreich's ataxia is an autosomal recessive congenital ataxia and is caused by a mutation in gene FXN (formerly known as X25) that codes for frataxin, located on chromosome 9. This protein is essential for proper functioning of mitochondria (it has been shown to be connected with the removal of iron from the cytoplasm surrounding themitochondria, and in the absence of frataxin, the iron builds up and causes free radical damage). Nerve and muscle cells appear to be particularly sensitive to the deleterious effects of this type of mitochondrial dysfunction.
The classic form of Friedreich's ataxia has been mapped to a gene on 9q13-q21 that affects production of the protein frataxin. In most cases, the mutant gene containsexpanded GAA triplet repeats in the first intron; in a few pedigrees, point mutations have been detected. Because the defect is located on an intron (which is removed from the mRNA transcript between transcription and translation), this mutation does not result in the production of abnormal frataxin proteins. Instead, the mutation causes gene silencing (i.e., the mutation decreases thetranscription of the gene) through induction of a heterochromatin structure in a manner similar to position-effect variegation.
Besides expression of frataxin, long tracts of GAA repeats induce chromosome breaks in vivo yeast studies.
 Relationship to muscular dystrophy
Friedreich's ataxia and the muscular dystrophy family of neuromuscular diseases, though often compared, are different diseases.Muscular dystrophies are the result of muscle tissue degeneration and atrophy, whereas Friedreich's ataxia is the result of nerve degeneration caused by a trinucleotide repeat expansion mutation. Research on both disorders is supported by funding from the Muscular Dystrophy Association
Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset FA mayoccur in the 20s or 30s. Symptoms include any combination, but not necessarily all, of the following:
* Muscle weakness in the arms and legs
* Loss of coordination
* Vision impairment
* Hearing impairment
* Slurred speech
* Curvature of the spine (scoliosis)
* High plantar arches (pes cavus deformity of the foot)
* Diabetes (about 20% of people with Friedreich's...
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