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 (FRDA)
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), biallelic GAA trinucleotide repeat expansion in intron 1 in ~96% of cases; ~4% are compound heterozygotes (one expansion plus a point variant or deletion)[1]
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: widespread repolarisation abnormality, particularly inferolateral T-wave inversion, in most patients; often the earliest cardiac finding and frequently present without LVH; LVH voltages; AF or atrial flutter with more advanced disease.[1][3]
Echocardiography: concentric, non-obstructive LVH and diastolic dysfunction; in the minority who progress, walls thin, the LV dilates and LVEF falls. Annual screening from diagnosis.[2][3]
Cardiac MRI: concentric remodelling or hypertrophy with increased LV mass; patchy mid-wall LGE appears with more advanced disease; LV mass may fall and LGE increase as the dilated phase develops. Fibrosis and falling LVEF mark the transition to end-stage disease.[2][3]
Troponin: chronic low-level elevation of cardiac troponin is common in Friedreich ataxia and does not by itself indicate an acute coronary syndrome; interpret against the patient's known baseline and the clinical picture.[4]
Ambulatory monitoring: for palpitations and in advanced cardiomyopathy, when AF and flutter become common.[4]
Glucose and HbA1c: diabetes affects a substantial minority and adds to cardiovascular risk.[4]
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
Burden: cardiac disease is the leading cause of death (~60% of deaths), usually through progressive heart failure and arrhythmia in the dilated phase; sudden death is less common but reported.[1][4]
Markers of poorer cardiac prognosis: longer GAA repeat length and earlier age of onset, LGE on CMR, falling LVEF with LV thinning and dilatation, and atrial arrhythmia.[1][3]
LVH is not the main risk marker: many patients have stable concentric hypertrophy for years; the transition to systolic dysfunction is the prognostic turning point, so serial LVEF matters more than wall thickness.[3]
Prognosis: progressive neurological disability, median survival 30s-40s
Pregnancy Management
mWHO class II–III or above: refer to a Pregnancy Heart Team before conception (see Pregnancy).
Pregnancy in Friedreich ataxia - individualised risk assessment
Cardiac risk in pregnancy is set by LV systolic function and arrhythmia history: women with preserved LVEF and concentric hypertrophy alone are usually at lower risk, while systolic dysfunction or atrial arrhythmia raises risk and needs Pregnancy Heart Team care.[5]
Pre-pregnancy assessment: ECG, echocardiography and, if symptomatic, ambulatory monitoring; review diabetes control, and mobility and falls risk as pregnancy advances.[4][5]
Medication: review all drugs for pregnancy safety; omaveloxolone is not recommended in pregnancy, and ACE inhibitors or ARBs used for LV dysfunction are stopped.[5]
Genetic considerations: autosomal recessive; with a non-carrier partner, all children of an affected parent are carriers; with a carrier partner, each child has a 50% chance of being affected and a 50% chance of being a carrier, so partner carrier testing informs counselling.[1]
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
- Cardiomyopathy may precede neurological symptoms[1]
- Distinguish from HCM - neurological features, family history, genetic testing
- Widespread T-wave inversion is common and may be the only cardiac finding[3]
- Chronic troponin elevation is common: interpret against the patient's baseline before diagnosing an acute coronary syndrome[4]
- Falling LVEF, not wall thickness, marks the prognostic turning point[3]
- Omaveloxolone slows neurological progression but does not treat the cardiomyopathy
- Annual cardiac screening (ECG, echo) from diagnosis[2]
References & Review Date
Last reviewed: October 2026
Key studies in Friedreich ataxia · the landmark studies, drawn to scale with the other inherited cardiac conditions.
- 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
- Weidemann F, Rummey C, Bijnens B, et al. The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms. Circulation. 2012;125(13):1626–1634. doi:10.1161/CIRCULATIONAHA.111.059477
- Corben LA, Lynch D, Pandolfo M, Schulz JB, Delatycki MB. Consensus clinical management guidelines for Friedreich ataxia. Orphanet J Rare Dis. 2014;9:184. doi:10.1186/s13023-014-0184-7
- De Backer J, Haugaa KH, et al. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy. Eur Heart J. 2025;46(43):4462–4568. doi:10.1093/eurheartj/ehaf193