Friedreich ataxia
Friedreich ataxia is an autosomal recessive trinucleotide (GAA) repeat disorder that silences the frataxin gene, causing mitochondrial iron accumulation and degeneration of the spinocerebellar and dorsal column tracts. It presents in childhood or adolescence with progressive gait ataxia, dysarthria, and loss of deep tendon reflexes, and its leading cause of death is hypertrophic cardiomyopathy. Diagnosis is by genetic testing; management is multidisciplinary and supportive.
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What this article covers
- Overview
Definition: Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by GAA trinucleotide repeat expansion in the frataxin (FXN) gene, producing progressive degeneration of the…
- Epidemiology
Most common inherited ataxia: Friedreich ataxia is the most frequent cause of hereditary ataxia in populations of European ancestry.
- Risk factors
Biallelic GAA expansion in FXN: the sole cause; both parents must carry at least one expanded allele for a child to be affected.
- Pathophysiology
GAA repeat expansion: an expanded GAA trinucleotide repeat in intron 1 of the FXN gene on chromosome 9 impairs normal transcription, markedly reducing production of frataxin, a small mitochondrial iron-binding protein.
- Clinical features
Progressive gait ataxia is the first sign of disease, typically beginning insidiously in late childhood or adolescence and gradually worsening.
- Differential diagnosis
Ataxia-telangiectasia: oculocutaneous telangiectasias, recurrent sinopulmonary infections, and elevated alpha-fetoprotein distinguish this ATM-gene disorder from the FXN-based pattern of Friedreich ataxia.
- Diagnosis
Diagnosis is established by genetic testing showing biallelic GAA trinucleotide repeat expansion in the FXN gene, which is the definitive confirmatory test; clinical findings alone are suggestive but not diagnostic.
- Management
There is no cure and no disease-modifying therapy established; management is lifelong, multidisciplinary, and centers on surveillance and treatment of the cardiac, endocrine, and skeletal…
- Complications
Hypertrophic cardiomyopathy and heart failure: the leading cause of death, from progressive myocardial fibrosis and arrhythmia.
- Prognosis
Progressive, life-shortening disease: most patients lose independent ambulation within about 10 to 15 years of symptom onset, though the pace varies with GAA repeat length.
- Prevention
No primary prevention exists for the underlying GAA expansion; prevention efforts focus on genetic counseling and early detection of complications.
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