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Friedreich ataxia
Epidemiology:
- most common inherited ataxia
Pathology:
1) hypertrophic cardiomyopathy
2) cardiac conduction defects
3) degeneration of spinal cord dorsal columns
4) degeneration of neurons in:
a) dorsal root ganglia
b) dentate nucleus of cerebellum
5) diabetes mellitus/carbohydrate intolerance
6) iron-sulfur cluster enzyme deficiency
- iron deposits in myocardium at autopsy
Genetics:
1) autosomal recessive
2) GAA trinucleotide expansion (100-1100) within the 1st intron of the frataxin (FRDA) gene resulting in severely decreased expression of frataxin
3) in some cases the disease is due to mutations in the coding region of frataxin (FRDA) Clinical manifeactions:
1) average age of onset is 10 years of age, usually manifest before adolescence
2) progressive gait & limb ataxia
3) dysarthria
4) areflexia of lower limbs
5) diminished vibratory sensation
6) lower extremity weakness
7) extensor plantar responses (Babinski's sign)
8) scoliosis, pes cavus, & hammer toe
Laboratory: FriedreichFriedreichFriedreichFriedreich- serum transferrin is increased
- FXN gene GAA repeats
Radiology:
- magnetic resonance imaging
- iron deposits in dentate nucleus
Management:
- amantadine may be of some value [2]
- omaveloxolone (Skyclarys) FDA-approved
Related
frataxin; Friedreich ataxia protein (FXN, FRDA, X25)
FRDA (frataxin) gene
General
cerebellar degeneration
developmental disorder
trinucleotide repeat expansion disease
Database Correlations
OMIM 229300
References
- Harrison's Principles of Internal Medicine, 13th ed.
Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1038
- OMIM 229300
- Durr. Lancet Neurology 1:370-4, 2002
- National Institute of Neurological Disorders and Stroke (NINDS)
NINDS Friedreich's Ataxia Information Page
https://www.ninds.nih.gov/Disorders/All-Disorders/Friedreichs-Ataxia-Information-Page