Friedreich's Ataxia
Summary
Friedreich's ataxia (FRDA) is the most common inherited ataxia, caused by a GAA trinucleotide repeat expansion in the FXN gene (chromosome 9), leading to frataxin deficiency. Frataxin is essential for mitochondrial iron handling; its deficiency causes oxidative damage to the nervous system, heart, and pancreas. Onset is typically in puberty (10-15 years). The classic presentation includes progressive ataxia with absent lower limb reflexes but upgoing plantars (mixed UMN/LMN signs), pes cavus, kyphoscoliosis, and cardiomyopathy (HOCM). Patients are typically wheelchair-bound by their 20s and die in their 30s-40s from cardiomyopathy or respiratory complications. There is no cure; management is supportive with annual cardiac and diabetic screening.
Key Facts
- Genetics: Autosomal recessive; GAA repeat in FXN gene (normal less than 33; disease >66)
- Protein: Frataxin (mitochondrial iron metabolism)
- Onset: 10-15 years (puberty)
- Neurological: Ataxia, Absent reflexes, Upgoing plantars, Sensory loss
- Systemic: HOCM (>90%), Diabetes, Pes cavus, Kyphoscoliosis
- Prognosis: Wheelchair by ~20s; Death 30s-40s (cardiomyopathy)
- No cure: Supportive management
Clinical Pearls
"Absent Reflexes + Upgoing Plantars = Think Friedreich's": This mixed picture (LMN absent reflexes from peripheral neuropathy + UMN upgoing plantars from spinocerebellar tract involvement) is classic for Friedreich's ataxia.
"Heart Kills Before the Brain": Hypertrophic cardiomyopathy is present in >90% and is the leading cause of death. Annual echocardiography is essential.
"Pes Cavus + Scoliosis + Ataxia": This triad in a young person should prompt consideration of Friedreich's ataxia.
"GAA Repeat Length Correlates with Severity": Longer GAA repeats (especially >800) correlate with earlier onset, more severe cardiomyopathy, and faster progression.
Why This Matters Clinically
Friedreich's ataxia is a devastating condition. Early diagnosis allows for cardiac and diabetic surveillance, genetic counselling, and supportive management to maximise quality of life.[1,2]
Incidence & Prevalence
| Parameter | Data |
|---|---|
| Prevalence | 1 in 50,000 (commonest inherited ataxia) |
| Carrier frequency | ~1 in 100 |
| Onset | Typically 10-15 years; Range 2-50 years |
Genetics
| Feature | Details |
|---|---|
| Gene | FXN (Frataxin) on chromosome 9q21 |
| Mutation | GAA trinucleotide repeat expansion (intron 1) |
| Normal repeats | 5-33 |
| Disease repeats | 66-1700 |
| Inheritance | Autosomal recessive |
Mechanism
| Step | Details |
|---|---|
| 1 | GAA expansion → Reduced frataxin transcription |
| 2 | Frataxin deficiency → Mitochondrial iron overload |
| 3 | Excess iron → Oxidative stress damage |
| 4 | Affected tissues: Dorsal root ganglia, Spinocerebellar tracts, Heart, Pancreas |
Neuropathology
| Structure | Degeneration |
|---|---|
| Dorsal root ganglia | Large sensory neurons → Sensory ataxia, Areflexia |
| Spinocerebellar tracts | Afferent pathways → Cerebellar ataxia |
| Corticospinal tracts | Later → Upgoing plantars, Spasticity |
| Cerebellum | Mild atrophy only |
Neurological Features
| Feature | Notes |
|---|---|
| Progressive gait ataxia | First symptom; Onset puberty |
| Limb ataxia | Arms affected later |
| Dysarthria | Cerebellar speech |
| Absent lower limb reflexes | Peripheral sensory neuropathy |
| Upgoing plantars | Corticospinal tract involvement (Babinski positive) |
| Sensory loss | Vibration and proprioception |
| Weakness | Later; Distal > Proximal |
Systemic Features
| Feature | Prevalence | Notes |
|---|---|---|
| Hypertrophic cardiomyopathy | >90% | Leading cause of death |
| Diabetes mellitus | 10-30% | Pancreatic involvement |
| Glucose intolerance | Common | |
| Pes cavus | 90% | High arched feet |
| Kyphoscoliosis | 80% | May require bracing/surgery |
| Optic atrophy | 25% | Visual loss |
Signs
| Sign | Notes |
|---|---|
| Absent knee/ankle reflexes | But upgoing plantars |
| Positive Romberg | Sensory ataxia |
| Wide-based gait | Ataxic |
| Finger-nose ataxia | Intention tremor |
| Dysdiadochokinesis | Impaired rapid alternating movements |
| Pes cavus | High arches |
| Scoliosis | Often severe |
Neurological Examination
| Test | Finding |
|---|---|
| Gait | Wide-based ataxic gait |
| Romberg | Positive (sensory ataxia) |
| Finger-nose | Intention tremor; Dysmetria |
| Heel-shin | Ataxic |
| Reflexes | Absent (lower limbs) |
| Plantars | Upgoing (Babinski positive) |
| Sensation | Reduced vibration and proprioception |
| Speech | Dysarthria (cerebellar) |
General Examination
- Pes cavus
- Kyphoscoliosis
- Cardiac exam (may reveal systolic murmur)
Genetic Testing
| Test | Purpose |
|---|---|
| FXN GAA repeat analysis | Diagnostic; >66 repeats in both alleles |
| Frataxin protein level | Reduced |
Cardiac
| Investigation | Purpose |
|---|---|
| ECG | LVH; T-wave inversion |
| Echocardiography | Hypertrophic cardiomyopathy; Annual surveillance |
| MRI heart | If echo difficult |
Other
| Investigation | Purpose |
|---|---|
| Fasting glucose / HbA1c | Screen for diabetes |
| Nerve conduction studies | Sensory axonal neuropathy |
| MRI spine | Cord atrophy |
Management Algorithm
FRIEDREICH'S ATAXIA MANAGEMENT
↓
┌───────────────────────────────────────────────────────────┐
│ DIAGNOSIS & GENETIC COUNSELLING │
├───────────────────────────────────────────────────────────┤
│ ➤ Genetic testing (FXN GAA repeat analysis) │
│ ➤ Family counselling (autosomal recessive) │
│ ➤ Carrier testing for at-risk relatives │
└───────────────────────────────────────────────────────────┘
↓
┌───────────────────────────────────────────────────────────┐
│ CARDIAC SURVEILLANCE │
├───────────────────────────────────────────────────────────┤
│ ⚠️ Cardiomyopathy is leading cause of death │
│ │
│ ➤ Annual echocardiography │
│ ➤ ECG annually │
│ ➤ Cardiology review if symptoms │
│ ➤ Treat heart failure if develops (ACEi, beta-blocker) │
│ ➤ ICD consideration if arrhythmia risk │
└───────────────────────────────────────────────────────────┘
↓
┌───────────────────────────────────────────────────────────┐
│ DIABETES SURVEILLANCE │
├───────────────────────────────────────────────────────────┤
│ ➤ Annual fasting glucose / HbA1c │
│ ➤ Treat diabetes per standard guidelines │
└───────────────────────────────────────────────────────────┘
↓
┌───────────────────────────────────────────────────────────┐
│ SUPPORTIVE CARE │
├───────────────────────────────────────────────────────────┤
│ PHYSIOTHERAPY: │
│ ➤ Balance and gait training │
│ ➤ Stretching (prevent contractures) │
│ ➤ Wheelchair prescription when needed │
│ │
│ OCCUPATIONAL THERAPY: │
│ ➤ Aids and adaptations │
│ ➤ Home environment modification │
│ │
│ SPEECH AND LANGUAGE: │
│ ➤ Dysarthria management │
│ ➤ Swallowing assessment in advanced disease │
│ │
│ ORTHOPAEDIC: │
│ ➤ Scoliosis bracing or surgery │
│ ➤ Foot surgery for pes cavus if needed │
└───────────────────────────────────────────────────────────┘
↓
┌───────────────────────────────────────────────────────────┐
│ EMERGING THERAPIES │
├───────────────────────────────────────────────────────────┤
│ ➤ Omaveloxolone (FDA-approved 2023): Nrf2 activator │
│ ➤ Gene therapy trials ongoing │
│ ➤ Antioxidants (idebenone — mixed evidence) │
└───────────────────────────────────────────────────────────┘
| Complication | Notes |
|---|---|
| Heart failure | From HOCM; Leading cause of death |
| Arrhythmias | May cause sudden death |
| Diabetes | Requires monitoring and treatment |
| Respiratory failure | In advanced disease; Restrictive pattern |
| Aspiration | Swallowing dysfunction |
| Immobility complications | Pressure sores; DVT |
| Factor | Outcome |
|---|---|
| Wheelchair use | By 10-15 years from onset |
| Life expectancy | Mean ~35 years; Range 20-50+ |
| Cause of death | Cardiomyopathy (~60%); Respiratory (~20%) |
| GAA repeat length | Longer = earlier onset, worse prognosis |
Key References
| Source | Notes |
|---|---|
| Ataxia UK | Patient support and guidelines |
What is Friedreich's ataxia?
Friedreich's ataxia is a rare inherited condition that causes problems with balance, coordination, and walking. It usually starts in childhood or teenage years and gets worse over time.
What causes it?
It's caused by a faulty gene (FXN) that makes a protein called frataxin. Without enough frataxin, certain parts of the brain and spinal cord, and the heart, are damaged.
What are the symptoms?
- Trouble walking and balance problems
- Slurred speech
- High-arched feet and curved spine
- Heart problems
- Diabetes
How is it treated?
There's no cure yet, but treatment can help manage symptoms:
- Physiotherapy for mobility
- Heart monitoring and treatment
- Diabetes management
- Wheelchairs and aids when needed
A new medicine called omaveloxolone has recently been approved to slow the disease.
- Lynch DR, Farmer JM, Balcer LJ, et al. Friedreich ataxia: effects of genetic understanding on clinical evaluation and therapy. Arch Neurol. 2002;59(5):743-747. PMID: 12020255
High-Yield Exam Topics
| Topic | Key Points |
|---|---|
| Genetics | AR; GAA repeat in FXN gene; Frataxin deficiency |
| Neuro signs | Ataxia + Absent reflexes + Upgoing plantars |
| Systemic | HOCM, Diabetes, Pes cavus, Scoliosis |
| Prognosis | Wheelchair by 20s; Death 30s-40s (heart) |
| Management | Surveillance; Supportive; Omaveloxolone |
Sample Viva Question
Q: A 14-year-old presents with ataxia. On examination they have absent knee jerks but upgoing plantars. What is the likely diagnosis and how would you manage?
Model Answer: The combination of absent reflexes (LMN from dorsal root ganglia degeneration) and upgoing plantars (UMN from corticospinal tract involvement) with ataxia in a teenager is classic for Friedreich's ataxia. I would look for pes cavus, scoliosis, and ask about family history.
Diagnosis: Genetic testing for GAA repeat expansion in FXN gene.
Management:
- Cardiac: Annual echocardiography (HOCM kills)
- Diabetes: Annual glucose/HbA1c screening
- Supportive: Physiotherapy, OT, SALT, orthopaedic input for scoliosis
- Emerging therapy: Omaveloxolone (FDA-approved 2023)
- Genetic counselling: For patient and family
Last Reviewed: 2025-12-24 | MedVellum Editorial Team