Makindo Medical Notes

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

About

• Friedreich's Ataxia (FA) is the most common of the hereditary spinocerebellar ataxias.
• It is an autosomal recessive disorder, with an incidence of 1 in 50,000 individuals.
• Onset typically occurs before the age of 25, though it may vary, with early signs often seen in adolescence.
• FA is characterized by progressive damage to the nervous system, leading to coordination and movement difficulties.

Aetiology

• Caused by an expanded GAA trinucleotide repeat in the FRDA gene on chromosome 9q13.
• The FRDA gene encodes a mitochondrial protein called frataxin, which is involved in iron homeostasis within mitochondria.
• Frataxin deficiency leads to mitochondrial iron overload, resulting in oxidative stress and cellular damage.
• This ultimately leads to progressive neurodegeneration, particularly in the spinocerebellar pathways, dorsal columns, and corticospinal tracts.

Pathophysiology

• Degeneration of the spinocerebellar tracts results in progressive loss of coordination and balance.
• The corticospinal tracts and dorsal columns are also affected, leading to weakness, spasticity, and sensory loss.
• Mitochondrial dysfunction and iron accumulation contribute to neurodegeneration and cardiomyopathy, a common complication of FA.

Clinical Features

• Progressive gait ataxia, typically the first symptom, with increasing difficulty in walking and maintaining balance.
• Clumsy hand movements, dysarthria (slurred speech), and muscle weakness.
• Characteristic foot deformities such as pes cavus (high-arched foot) and progressive kyphoscoliosis.
• Cerebellar signs including intention tremor, nystagmus, scanning speech, and incoordination.
• Optic atrophy in approximately 30% of patients, leading to vision problems.
• Peripheral neuropathy with areflexia (loss of deep tendon reflexes), resulting from damage to large sensory fibers.
• Cardiomyopathy, including left ventricular hypertrophy and fibrosis, can lead to heart failure or arrhythmias.
• Type 1 diabetes mellitus or impaired glucose tolerance in some cases.
• Upper motor neuron signs such as spastic paraparesis, extensor plantar responses (Babinski sign), and brisk reflexes.
• Dorsal column involvement leads to loss of vibration sense and proprioception, contributing to sensory ataxia.
• Sensorineural hearing loss, often progressive.
• Cardiac murmurs and signs of heart failure are often detectable, especially in advanced stages.

Investigations

• Genetic Testing: DNA testing to confirm the presence of GAA trinucleotide repeats on chromosome 9.
• MRI of the Brain and Spinal Cord: Shows atrophy of the cerebellum and spinal cord.
• EMG and Nerve Conduction Studies (NCS): Demonstrate sensory neuropathy, particularly affecting large myelinated fibers.
• Cardiac Evaluation: ECG and echocardiogram to assess for hypertrophic cardiomyopathy or conduction abnormalities.
• Fasting Blood Glucose and HbA1c: To evaluate for diabetes or impaired glucose tolerance.

Management

• There is no curative treatment for Friedreich's Ataxia; management focuses on supportive care and symptomatic relief.
• Multidisciplinary Approach: Involves neurologists, cardiologists, endocrinologists, physiotherapists, and occupational therapists.
• Physiotherapy: Helps maintain mobility, reduce spasticity, and prevent contractures.
• Occupational Therapy: Assists with daily living activities and adaptive equipment.
• Speech and Language Therapy: Useful for managing dysarthria and swallowing difficulties.
• Cardiac Monitoring and Management: Regular monitoring of heart function, with medications (e.g., beta-blockers, ACE inhibitors) for cardiomyopathy and arrhythmias.
• Diabetes Management: Insulin therapy and diet modifications for patients with diabetes.
• Genetic Counseling: Important for families to understand inheritance patterns and risks for future generations.
• Wheelchair Use: Most patients become wheelchair-bound by the second decade of life, due to progressive loss of mobility.
• DVT Prophylaxis: As immobility increases, thromboprophylaxis may be required.
• Life expectancy is reduced, typically between 40 and 50 years, primarily due to cardiac complications such as heart failure or arrhythmias.