Monogenic (Mendelian): ~100%, biallelic pathogenic FXN variants; approximately 96% have biallelic GAA-repeat expansions, approximately 4% have one expansion plus another pathogenic sequence variant or deletion[1]
Friedreich Ataxia
Quick Summary
Definition: An autosomal recessive disorder caused by an FXN GAA-repeat expansion, characterised by progressive ataxia and a cardiomyopathy that typically begins with concentric left ventricular hypertrophy and may progress to systolic dysfunction.[1]
- Prevalence: 1 in 50,000 (most common inherited ataxia), onset childhood/adolescence[1]
- Key gene: FXN (frataxin), autosomal recessive - GAA repeat expansion, mitochondrial dysfunction
- Hallmark: Progressive ataxia + areflexia + LVH (60-75%, concentric/symmetric) + diabetes + scoliosis
- High-risk markers: Severe LVH, systolic dysfunction, arrhythmias, early onset cardiac involvement
- First-line Mx: No disease-modifying therapy for the cardiomyopathy, which is managed with standard heart-failure care; omaveloxolone (Skyclarys, Nrf2 activator; FDA 2023, EMA 2024, MHRA 2025; ≥16yr) slows neurological progression but does not treat the cardiomyopathy, and is not routinely funded on the NHS; manage diabetes; physiotherapy for ataxia
Aetiology
Genetics
Inheritance: Autosomal recessive, both parents are obligate carriers of a GAA expansion or pathogenic FXN variant.[1]
Familial proportion: Nearly 100% of cases are inherited (de novo cases exceptionally rare). Siblings of an affected individual have a 25% risk of being affected; parents are carriers (unaffected). Carrier frequency ~1 in 85–100 in European populations.[1]
Gene: FXN (frataxin), homozygous GAA trinucleotide repeat expansion in intron 1 in ~96% of cases; ~4% are compound heterozygotes (one expansion + one point mutation)
Pathophysiology: Frataxin deficiency → mitochondrial iron accumulation → oxidative stress → cardiomyocyte and neuronal injury
Prevalence
Estimated prevalence 1 in 50,000, the most common inherited ataxia in European populations.[1]
Carrier frequency approximately 1 in 85–100 in European populations.[1]
Cardiomyopathy develops in 60–75% of affected individuals and is the leading cause of premature death.[2]
Onset typically in childhood or adolescence (mean age ~10–15 years).
Diagnosis
Confirming the diagnosis: genetic testing for a homozygous GAA trinucleotide-repeat expansion in FXN is diagnostic (a minority are compound heterozygous with a point variant). Larger repeat lengths correlate with earlier onset and a higher risk of cardiomyopathy.[1]
Neurological: Progressive ataxia, dysarthria, areflexia, proprioception loss
Cardiac (~60-75% have cardiomyopathy):
- Concentric LVH (symmetric, non-obstructive)
- Diastolic dysfunction
- Arrhythmias (atrial fibrillation, ventricular ectopy)
- Progressive to dilated phase in some (poor prognosis)
Other: Diabetes, scoliosis, pes cavus
Investigations
ECG: LVH, T-wave inversion, short PR interval (in some cases)[1]
Echo: Concentric LVH (non-obstructive), diastolic dysfunction, annual screening from diagnosis[2]
Cardiac MRI: Hypertrophy pattern, late gadolinium enhancement (fibrosis marker, prognostic significance)[2]
Genetic testing: FXN GAA repeat analysis (diagnostic)[1]
Treatments
1. General measures:
- Physiotherapy, occupational therapy, diabetes management
- Genetic counselling and family cascade testing, see the Genetic Testing page
2. Medical therapy:
- Omaveloxolone (Skyclarys): Nrf2 activator; FDA-approved February 2023, EMA-approved June 2024, MHRA-approved April 2025; indicated for patients ≥16 years with Friedreich ataxia; slows neurological progression but does not treat the cardiomyopathy. UK access: not routinely funded on the NHS. The NICE appraisal did not reach a recommendation after the manufacturer withdrew its evidence submission, and the Scottish Medicines Consortium did not recommend it in March 2026; individual funding request routes exist in some UK nations. Confirm the current position locally, as this is changing
- Standard therapy for the HCM phenotype/heart failure as appropriate; treat arrhythmias, heart failure
3. Device therapy:
- Pacing/ICD per standard indications if conduction disease or arrhythmia develops
4. Advanced heart failure and/or transplant referral:
- Standard advanced-heart-failure pathways apply if cardiomyopathy progresses to refractory heart failure, individualised alongside the neurological/functional prognosis
Complications
Risk Stratification
Cardiac disease major cause of death (~60% of deaths)
Prognosis: Progressive neurological disability, median survival 30s-40s
Follow-up
Based on ESC 2023 Cardiomyopathy guidelines and Friedreich ataxia reviews[2][1].
Advanced / complicated = LVEF decline or systolic dysfunction, AF, or symptomatic heart failure.
| Uncomplicated / Stable | Advanced / Complicated | |
|---|---|---|
| Frequency | Annual | Every 6 months |
| Clinical review | Symptoms, HF signs (may be limited by ataxia) | As above |
| ECG | Annual 12-lead (widespread T-wave changes) | Each visit |
| Echocardiography | Annual (LV mass, function) | 6-monthly |
| Holter / ambulatory | Periodic (AF common with LV dysfunction) | As indicated |
Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.
Key Points
References & Review Date
Last reviewed: July 2026
- Schulz JB, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective. Nat Rev Neurol. 2009;5(4):222–234. doi:10.1038/nrneurol.2009.26
- Arbelo E, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503–3626. doi:10.1093/eurheartj/ehad194