Orthopedic Surgery for Friedreich Ataxia

Updated: Sep 08, 2017
  • Author: Stephen Kishner, MD, MHA; Chief Editor: Harris Gellman, MD  more...
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Overview

Background

Friedreich ataxia (FA) is the prototype of all forms of progressive ataxia, and it accounts for approximately one half of all cases of hereditary ataxia. FA is an autosomal recessive spinocerebellar disorder that has a slow but relentlessly degenerative course. [1, 2]

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Pathophysiology and Etiology

FA is an autosomal recessive disorder caused by a mutation and abnormal expansion of a GAA repeat in intron 1 of the FXN gene, which is located on chromosome 9. This gene encodes a 210-amino-acid protein called frataxin. The pathology in FA results from lack of frataxin or its function.

Certain nerve and muscle cells cannot function properly with a shortage of frataxin, leading to the signs and symptoms of FA. Approximately 98% of mutant alleles have an expansion of a gossypol acetic acid (GAA) trinucleotide repeat in intron 1 of the gene, leading to reduced levels of frataxin. [3, 4, 5, 6, 7, 8, 9, 10]

The current hypothesis is that frataxin is a mitochondrial protein important for normal production of cellular energy. A defect in its action may result in abnormal accumulation of iron in mitochondria, leading to excess production of free radicals, which then results in cellular damage and death. [11]  The neural pathways affected in FA are those associated with large neuronal cell bodies and extensive axon elongations, which are the long tracts of the dorsal columns, pyramidal system, and peripheral nerves.

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Epidemiology

FA occurs in 1-2 per 100,000 of the US population. Its international prevalence is also 1-2 per 100,000; prevalence appears to be slightly higher in Quebec, Canada.

Symptoms may begin in infancy or in the third decade; however, symptoms usually begin when an individual is aged 8-15 years. Men and women are affected equally. All races are affected.

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Prognosis

The rate of progression of FA is variable. The rate of progression of FA is variable, but more than 95% of individuals with FA cannot ambulate by the time they are aged 45 years, and on average, patients lose the ability to walk 15 years following onset of symptoms. The mean age of loss of ambulation is 25 years. 

Age at death is rather variable. Death usually occurs in the middle of the fourth decade of life. However, survival into the sixth and seventh decades of life has been documented. Death often is related to cardiomyopathy and diabetes and tends to occur earleir when these conditions are present, but aspiration pneumonia due to dysphagia also may shorten the lifespan of patients with FA.

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Patient Education

Patients and their parents must be provided with information on the nature, inheritance, and implications of the genetic disorder to help them make informed medical and personal decisions.

FA is inherited in an autosomal recessive manner. Parents of a child diagnosed with FA are both obligate carriers of an FXN gene mutation. Siblings of patients with FA have a 25% risk of being affected. Offspring of patients with FA all inherit one mutant allele from the affected parent. However, these children only have a risk of being affected if the unaffected parent is a carrier of a mutation in the FXN gene. The carrier status of the unaffected parent can be determined by DNA testing.

Patients should be instructed as to the importance of maintaining an active lifestyle.

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