Friedreich Ataxia
The Most Common Hereditary Ataxia
Key Features
Critical Must-Knows
- FXN Gene: GAA trinucleotide repeat expansion.
- Cardiomyopathy: Leading cause of death.
- Scoliosis: Progressive, often requires fusion.
- Cavovarus Feet: Common, similar to CMT.
- Wheelchair Dependency: Usually by 15 years after onset.
Examiner's Pearls
- "GAA repeat in FXN gene
- "Cardiomyopathy is main mortality cause
- "Scoliosis surgery has cardiac risks
- "Similar foot deformity to CMT
Critical Cardiac Risks in Friedreich Ataxia
Leading Cause of Death
Hypertrophic Cardiomyopathy is the main cause of mortality. Sudden cardiac death can occur. Arrhythmias and heart failure are common.
Pre-Op Mandatory
Cardiology Clearance with recent Echocardiogram and ECG is ESSENTIAL before any orthopaedic surgery (especially scoliosis fusion).
Anesthesia Alert
Anesthesia team must be aware of cardiomyopathy. Fluid management (preload maintenance) is critical to prevent cardiac decompensation.
Friedreich Ataxia vs CMT
| Feature | Friedreich Ataxia | CMT |
|---|---|---|
| Autosomal Recessive | Autosomal Dominant (usually) | |
| Spinocerebellar | Peripheral nerve | |
| Cardiomyopathy (major) | Not affected | |
| 80-100% | Rare | |
| Cavovarus | Cavovarus |
Friedreich Ataxia Features
Memory Hook:FACS - FXN, Ataxia, Cardiomyopathy, Scoliosis.
Orthopaedic Issues
Memory Hook:SF - Spine and Feet.
Pre-Op Checklist
Memory Hook:CRD - Cardiac, Respiratory, Diabetes.
Overview/Epidemiology
Friedreich Ataxia (FA) is the most common hereditary ataxia.
- Genetics: Autosomal recessive. GAA trinucleotide repeat expansion in the FXN gene on chromosome 9.
- Incidence: 1 in 50,000.
- Onset: Usually 5-15 years. Earlier onset = more severe.
- Pathophysiology: Frataxin deficiency leads to mitochondrial dysfunction and iron accumulation in cells.
Pathophysiology
Neurological Pathology
- Degeneration of spinocerebellar tracts, dorsal columns, and peripheral nerves.
- Results in ataxia, sensory loss, and weakness.
- Pyramidal signs late (Babinski positive despite absent reflexes).
Why Scoliosis Develops
- Combination of truncal weakness and ataxia.
- Curve patterns variable (unlike neuromuscular scoliosis).
- Often progresses rapidly, especially in wheelchair users.
Cavovarus Feet
- Similar mechanism to CMT (muscle imbalance).
- May precede neurological symptoms.
Classification Systems
Neurological Features
- Gait Ataxia: Often the first symptom. Progressive.
- Limb Ataxia: Intention tremor, dysmetria.
- Dysarthria: Slurred speech.
- Reflexes: Absent tendon reflexes with positive Babinski.
- Sensory Loss: Proprioception and vibration affected.
- Wheelchair Dependency: Usually by 10-15 years after onset.
Clinical Assessment
History:
- Age of onset.
- Progression of ataxia.
- Cardiac symptoms (palpitations, syncope).
- Family history.
- Mobility status.
Physical Exam:
- Gait: Wide-based, ataxic.
- Reflexes: Absent with positive Babinski.
- Sensory: Reduced proprioception, vibration.
- Spine: Scoliosis assessment.
- Feet: Cavovarus, claw toes.
- Cardiac: Listen for murmurs.
Investigations
Genetic Testing:
- FXN gene GAA repeat expansion: Confirmatory.
Cardiac:
- Echocardiogram: Assess for hypertrophic cardiomyopathy.
- ECG: Arrhythmias.
Metabolic:
- HbA1c, glucose: Diabetes screening.
Imaging:
- Spine X-ray: Scoliosis.
- Foot X-ray: Cavovarus assessment.
Management Algorithm
Scoliosis Management
- Observation: For mild curves.
- Bracing: May slow progression but does not prevent it.
- Surgery: Posterior spinal fusion for curves greater than 40-50 degrees.
- Cardiac Clearance: Essential before surgery.
Surgical Techniques
Posterior Spinal Fusion
Indications: Progressive scoliosis greater than 40-50 degrees.
Pre-op: Cardiology clearance mandatory. Echocardiogram. Anesthesia team experienced with cardiomyopathy.
Technique: Posterior approach. Fusion extent depends on curve (often T2-L4 or pelvis if sitting). Pedicle screw constructs.
Post-op: ICU monitoring. High perioperative risk due to cardiac disease.
Complications
| Complication | Context | Management |
|---|---|---|
| Cardiac Arrhythmia/Sudden Death | Intra/postoperative | Cardiac monitoring, experienced team |
| Respiratory Compromise | Surgery, disease progression | Careful anesthesia, postop monitoring |
| Scoliosis Progression | Even after fusion at end of construct | Monitor |
| Foot Deformity Recurrence | Progressive disease | Monitor, revise |
Postoperative Care
- ICU Monitoring: Cardiac telemetry.
- Early Mobilization: As tolerated.
- Physiotherapy: Maintain function.
- Long-Term: Cardiology follow-up, orthotic use.
Outcomes/Prognosis
- Life Expectancy: Median 30-40 years. Cardiac disease is the main determinant.
- Wheelchair Dependency: Usually 10-15 years after symptom onset.
- Scoliosis Surgery: Improves sitting, may prevent respiratory decline.
- Disease Progression: Relentless. No cure currently.
Evidence Base
- Scoliosis in Friedreich Ataxia
- High progression rate
- Fusion improves sitting balance
- Natural history of scoliosis in FA
- Rapid progression
- Early fusion recommended
- Comprehensive review of FA
- Cardiac disease is major issue
- No disease-modifying therapy yet
- Outcomes of scoliosis surgery in FA
- High complication rate but worthwhile
- Cardiac clearance essential
- Discovery of FXN gene
- GAA repeat expansion
- Foundation for genetic testing
Viva Scenarios
Practice these scenarios to excel in your viva examination
Scoliosis in Friedreich Ataxia
"12-year-old with confirmed Friedreich Ataxia. Thoracolumbar scoliosis of 55 degrees. Ambulant with assistance. Known hypertrophic cardiomyopathy on echo."
This patient needs **scoliosis surgery** given the 55-degree curve and progressive disease. However, the **cardiomyopathy is a major concern**. Pre-operatively, I would ensure **cardiology clearance** with recent echo and ECG. The anesthesia team must be experienced in managing cardiomyopathy (avoid hypovolemia, maintain preload). I would perform **posterior spinal fusion** (likely T2-L4 or lower depending on curve). Postoperatively, **ICU monitoring with telemetry** is essential. I would counsel the family about the increased surgical risk.
Cavovarus Feet in FA
"Same patient also has bilateral cavovarus feet with claw toes. Coleman block test is positive."
The cavovarus feet are managed similarly to CMT. The **positive Coleman block test** indicates the deformity is **supple**. I would perform **soft tissue surgery**: plantar fascia release, first metatarsal dorsiflexion osteotomy, peroneus longus to brevis transfer, and claw toe correction (Jones procedure). Given the progressive nature of FA, recurrence is possible. Post-op orthotic use is important.
Genetics of FA
"What is the genetic cause of Friedreich Ataxia?"
Friedreich Ataxia is caused by a **GAA trinucleotide repeat expansion** in the **FXN gene** on chromosome 9. This gene encodes **frataxin**, a mitochondrial protein. Frataxin deficiency leads to iron accumulation and mitochondrial dysfunction, causing cell death particularly in the nervous system and heart. The inheritance is **autosomal recessive**.
MCQ Practice Points
Genetics MCQ
Q: What is the genetic mutation in Friedreich Ataxia? A: GAA trinucleotide repeat expansion in the FXN gene.
Cardiac MCQ
Q: What cardiac condition is most associated with FA? A: Hypertrophic cardiomyopathy.
Orthopaedic MCQ
Q: What percentage of FA patients develop scoliosis? A: 80-100%.
Prognosis MCQ
Q: What is the leading cause of death in FA? A: Cardiac disease (cardiomyopathy, arrhythmias).
Neurological MCQ
Q: What is the unique reflex finding in FA? A: Absent deep tendon reflexes with positive Babinski sign (pyramidal signs with peripheral neuropathy).
Scoliosis Surgery MCQ
Q: What is essential before scoliosis surgery in FA? A: Cardiology clearance with echocardiogram and ECG to assess cardiomyopathy.
Australian Context
- Genetic Testing: Available through clinical genetics.
- Multidisciplinary Care: Neurology, cardiology, orthopaedics.
- Scoliosis Surgery: High-risk, done at specialized centers.
- Support Groups: Friedreich Ataxia Network.
FRIEDREICH ATAXIA
High-Yield Exam Summary
GENETICS
- •FXN Gene
- •GAA repeat
- •Autosomal Recessive
- •Frataxin deficiency
CLINICAL
- •Progressive ataxia
- •Absent reflexes + Babinski
- •Cardiomyopathy
- •Diabetes
ORTHOPAEDIC
- •Scoliosis 80-100%
- •Cavovarus feet
- •Similar to CMT management
- •High surgical risk
CARDIAC
- •Hypertrophic cardiomyopathy
- •Leading cause of death
- •Arrhythmias
- •Pre-op echo mandatory
SCOLIOSIS SURGERY
- •T2-L4 or pelvis fusion
- •Cardiology clearance
- •ICU monitoring
- •High perioperative risk
PROGNOSIS
- •Median survival 30-40 yrs
- •Wheelchair by 10-15 yrs
- •No cure currently
- •Multidisciplinary care
Self-Assessment Quiz
Differential Diagnosis
Other Causes of Hereditary Ataxia:
- Spinocerebellar Ataxias (SCA): Multiple types, autosomal dominant, different gene mutations.
- Ataxia-Telangiectasia: Telangiectasias, immunodeficiency, radiosensitivity.
- Vitamin E Deficiency: Acquired or genetic (AVED), similar phenotype, treatable.
Key Differentiators for Friedreich Ataxia:
- Autosomal recessive inheritance.
- GAA repeat in FXN gene is confirmatory.
- Cardiomyopathy is unique to FA among hereditary ataxias.
- Absent reflexes with positive Babinski.
Red Flags Requiring Investigation:
- Asymmetric presentation - investigate other causes.
- Rapid progression - consider alternative diagnosis.
- Positive family history of dominant pattern.