Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

🧬 Friedreich's Ataxia (FA) is the most common hereditary spinocerebellar ataxia. It is an autosomal recessive disorder (1 in 50,000), usually beginning in adolescence. FA causes progressive damage to the nervous system, leading to movement problems, sensory loss, and systemic complications such as cardiomyopathy and diabetes.

🧾 Aetiology

• 🔁 Caused by expanded GAA trinucleotide repeats in the FRDA gene (chromosome 9q13).
• Encodes frataxin, a mitochondrial protein regulating iron metabolism.
• Frataxin deficiency → mitochondrial iron overload → oxidative stress → neuronal and cardiac cell death.
• Mainly affects spinocerebellar tracts, dorsal columns, and corticospinal tracts.

⚙️ Pathophysiology

• Spinocerebellar degeneration → progressive gait ataxia and poor coordination.
• Corticospinal involvement → spasticity, weakness, Babinski sign.
• Dorsal column damage → impaired proprioception and vibration sense → sensory ataxia.
• Mitochondrial dysfunction → hypertrophic cardiomyopathy (major cause of morbidity and mortality).

🧑‍⚕️ Clinical Features

• 🚶‍♂️ Progressive gait ataxia – usually first symptom.
• 🤲 Clumsy hand movements, dysarthria (slurred speech), and limb weakness.
• 👣 Foot deformities: pes cavus, hammer toes; spinal deformities: scoliosis/kyphosis.
• 👁️ Optic atrophy (≈30%), nystagmus, scanning speech.
• 🔔 Loss of deep tendon reflexes but upgoing plantars (mixed LMN + UMN signs).
• 📉 Loss of vibration/proprioception (dorsal column disease).
• 🫀 Cardiomyopathy → arrhythmias, heart failure, murmurs.
• 🍬 Diabetes mellitus or glucose intolerance in some patients.
• 👂 Progressive sensorineural hearing loss.

🧪 Investigations

• 🧬 Genetic Testing: confirms GAA repeat expansion on FRDA gene.
• 🧲 MRI: atrophy of cerebellum and spinal cord.
• ⚡ EMG/NCS: large-fibre sensory neuropathy.
• 🫀 Cardiac: ECG + echo for LV hypertrophy or conduction block.
• 🩸 Bloods: FBC, HbA1c/glucose for diabetes screening.

🛠️ Management

• ❌ No cure – management is supportive and multidisciplinary.
• 🧑‍⚕️ MDT Care: neurologist, cardiologist, endocrinologist, physio, OT, speech therapy.
• 🏃‍♂️ Physio & OT: maintain mobility, reduce contractures, assistive devices.
• 🗣️ Speech therapy: for dysarthria and swallowing support.
• 🫀 Cardiac: regular monitoring; beta-blockers, ACE inhibitors, arrhythmia management.
• 🍬 Diabetes: insulin therapy, diet modification if required.
• 🧬 Genetic counselling: crucial for families.
• ♿ Mobility: most patients require a wheelchair within 10–20 years of onset.
• 🩸 DVT prophylaxis: in immobile patients.
• ⏳ Prognosis: life expectancy shortened (40–50 yrs), most deaths due to cardiomyopathy/arrhythmia.

💡 Clinical Tips

• Combination of ataxia + absent reflexes + extensor plantars is a classic exam clue.
• Always check for pes cavus and scoliosis – often overlooked but strongly suggest FA.
• Cardiac involvement is the major determinant of survival.

📚 References

• NIH: Friedreich’s Ataxia
• NORD – Friedreich’s Ataxia
• StatPearls: Friedreich’s Ataxia

Cases — Friedreich’s Ataxia

• Case 1 — Teenager with Progressive Gait Ataxia 🚶: A 15-year-old boy develops clumsiness, frequent tripping, and difficulty with balance. Exam: wide-based gait, absent ankle reflexes, impaired vibration sense, and pes cavus. Family history: cousin with similar condition. Diagnosis: Friedreich’s ataxia (autosomal recessive). Management: Supportive — physiotherapy, orthotics, genetic counselling.
• Case 2 — Ataxia with Cardiomyopathy ❤️: A 19-year-old woman with known Friedreich’s ataxia presents with palpitations and shortness of breath. ECG: left ventricular hypertrophy; echocardiogram: hypertrophic cardiomyopathy. Diagnosis: Friedreich’s ataxia complicated by hypertrophic cardiomyopathy. Management: Cardiology input (β-blockers/CCB, arrhythmia surveillance); MDT follow-up.
• Case 3 — Neurological + Endocrine Features 🩸: A 24-year-old man with Friedreich’s ataxia reports worsening balance and hand incoordination. Exam: dysarthria, scoliosis, distal wasting. Bloods: HbA1c 78 mmol/mol (new diabetes). Diagnosis: Friedreich’s ataxia with diabetes mellitus. Management: Endocrinology referral; lifestyle + insulin; ongoing neurorehabilitation.

Teaching Commentary 🧠

Friedreich’s ataxia is an autosomal recessive GAA trinucleotide repeat expansion in the frataxin gene. Onset usually in adolescence. Key features: - Progressive gait + limb ataxia, dysarthria, loss of vibration/proprioception, areflexia. - Skeletal: pes cavus, scoliosis. - Cardiac: hypertrophic cardiomyopathy, arrhythmias (major cause of death). - Endocrine: diabetes mellitus. Diagnosis: genetic testing. MRI shows spinal cord and cerebellar atrophy. Management: supportive MDT care — physio, orthotics, cardiology, diabetes management, genetic counselling. Life expectancy: reduced (death often in 30s–40s from cardiac disease).