Friedreich Ataxia

Friedreich ataxia is the most common inherited ataxia, affecting approximately 1 in 50,000 people. The mutation is present in approximately 1 in 120 people. Although onset is most commonly in childhood, adult-onset cases (>age 20) constitute up to 25% of all cases of FA. Late-onset disease is usually associated with less severe symptoms and slower progression.

Inheritance
Autosomal recessive; no anticipation.

Molecular genetics and pathogenesis
The frataxin gene encodes a mitochondrial iron transport protein. The most common mutation (97% of cases) is a GAA expansion. The normal repeat length is 5-30 trinucleotides, while disease genes harbor 70 to more than 1,000. Mutation causes accumulation of iron in mitochondria. The severity of the disease correlates with the repeat number in the less expanded allele.

Clinical manifestations
Limb ataxia, speech difficulty, involuntary eye movements, reduced reflexes, abnormal enlargement of the heart (hypertrophic cardiomyopathy), diabetes, scoliosis. Patients diagnosed with FA need to be actively screened for the presence of cardiomyopathy and diabetes.

Treatment
A recent randomized, double-blind trial of idebenone in childhood FA indicates this antioxidant improves neurologic function. The dose used was up to 45 mg/kg/day. Previous studies have confirmed the potential of this treatment for improvement of cardiomyopathy.

References
Friedreich ataxia entry in OMIM
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=229300

Di Prospero NA, Baker A, Jeffries N, Fischbeck KH. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial. Lancet Neurol. 2007 Oct;6(10):878-886.
PMID: 17826341

	Fragile X Tremor/Ataxia Syndrome (FXTAS)