Friedreich Ataxia

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.

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.

The topic states "frataxin deficiency leads to mitochondrial dysfunction and iron accumulation" without the mechanism that links the gene to the multisystem phenotype - examinable basic science.

• What the GAA expansion does. The expanded GAA repeat in the first intron of FXN causes heterochromatin/transcriptional silencing, so the gene is switched down rather than mutated - a quantitative deficiency of structurally normal frataxin. This is why FA is recessive (both alleles reduced) and why a larger repeat → less frataxin → earlier, more severe disease.
• What frataxin does. Frataxin is a mitochondrial protein essential for the biogenesis of iron-sulphur (Fe-S) clusters and for safe mitochondrial iron handling/storage.
• The downstream lesion. Frataxin deficiency impairs Fe-S-cluster-dependent enzymes - mitochondrial aconitase and respiratory-chain complexes I-III - and causes mitochondrial iron accumulation and oxidative stress, producing an energy-deficit/oxidative cell injury.
• Why these particular tissues. The damage falls on high-energy-demand, iron-handling tissues, explaining the multisystem pattern: large sensory neurons of the dorsal root ganglia and the dorsal columns, spinocerebellar and corticospinal tracts (ataxia, proprioceptive loss, areflexia with extensor plantars), cardiomyocytes (hypertrophic cardiomyopathy), pancreatic beta cells (diabetes), and the optic and auditory pathways.

So a single mitochondrial energy/iron defect produces the neurological, cardiac, metabolic AND skeletal picture - and the therapeutic logic (e.g. the Nrf2 activator omaveloxolone targeting oxidative stress) follows from it.

The topic repeatedly names "hypertrophic cardiomyopathy" as the leading cause of death and demands cardiology clearance, but never develops what the cardiomyopathy actually is - which matters because it drives both mortality and the perioperative risk the topic stresses.

• What it is. A concentric, usually NON-obstructive hypertrophic cardiomyopathy (unlike sarcomeric HOCM there is typically no left-ventricular outflow-tract obstruction), reflecting the cardiomyocyte energy deficit. It is common and often subclinical early, and it correlates with larger GAA repeats / earlier onset.
• The natural history. Many hearts later transition to a dilated, "burnt-out" phase with systolic dysfunction, and it is this systolic failure and arrhythmia - especially atrial fibrillation/flutter and ventricular arrhythmias - that cause death; FA is the leading cause of mortality in the disease.
• Surveillance. Periodic ECG, echocardiography (and Holter for arrhythmia) detect the hypertrophy, falling ejection fraction and rhythm disturbance before they become symptomatic.
• Management. There is no FA-specific cardiac cure (omaveloxolone is for the neurological phenotype); management is symptom-based - standard heart-failure therapy as systolic function declines and anticoagulation/rate-or-rhythm control for atrial fibrillation, with device therapy in selected cases.
• Why the surgeon cares. Because the cardiomyopathy is usually non-obstructive with preserved systolic function early, a fusion is not absolutely contraindicated, but the anaesthetic plan must maintain preload/afterload and avoid tachyarrhythmia (TIVA, intra-operative echo, meticulous fluid management) - the perioperative caution this topic emphasises. (Detailed cardiology is beyond the orthopaedic remit and is managed by the cardiology team.)

• ICU Monitoring: Cardiac telemetry.
• Early Mobilization: As tolerated.
• Physiotherapy: Maintain function.
• Long-Term: Cardiology follow-up, orthotic use.

• 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.

Global Epidemiology

• Most common inherited ataxia in populations of European, Middle Eastern, South Asian and North African descent; prevalence roughly 1 in 50,000, carrier frequency around 1 in 60-90.
• Effectively absent in populations of Sub-Saharan African and East Asian origin — a useful exam discriminator pointing away from FA.
• Larger GAA expansions broadly correlate with earlier onset, more frequent cardiomyopathy and diabetes, and faster progression to wheelchair use.

Side-by-Side Practice

Registry & Resource Notes

• No dedicated arthroplasty/implant registry captures FA spinal surgery; evidence rests on single-centre and two-centre series, so outcomes data are inherently limited.
• High-resource settings: TIVA, intraoperative echocardiography, multimodal monitoring and ICU/ECMO backup.
• Limited-resource settings: prioritise cardiac risk stratification and a planned wake-up test where advanced neuromonitoring is unavailable; concentrate care in referral centres.
• Patient organisations (e.g. Friedreich's Ataxia Research Alliance, Ataxia UK) support genetic counselling and multidisciplinary care coordination.