Neuroscience · Year 2 · from Neuroscience
Case 2: Friedreich Ataxia
Patient Presentation
Demographics: 16-year-old male
Chief Complaint: Progressive difficulty walking and clumsiness for 3 years
History of Present Illness: A 16-year-old boy is brought in by his parents for evaluation of gradually worsening balance and coordination. He began having trouble with sports around age 13, initially attributed to "growing pains." Over the past two years, his gait has become progressively unsteady, and he now uses walls for support when walking. He has developed difficulty with handwriting, which has become larger and more irregular. He also reports frequent stumbling on stairs and difficulty buttoning shirts. His speech has become slightly slurred according to his parents. He denies double vision, weakness, or sensory symptoms. Family history reveals a younger sister with similar but milder symptoms.
Physical Examination:
- Vital signs: Normal; cardiac examination reveals systolic murmur
- General: Thin adolescent male; kyphoscoliosis noted
- Neurological:
- Mental status: Normal intelligence and cognition
- Cranial nerves: Dysarthria; horizontal nystagmus; no ophthalmoplegia
- Motor: Mild distal leg weakness (4/5 ankle dorsiflexion bilaterally); no atrophy
- Sensory: Decreased vibration and proprioception at ankles and fingers; normal pain and temperature
- Reflexes: ABSENT throughout (areflexia)
- Coordination: Severe bilateral limb ataxia; dysmetria on finger-to-nose and heel-to-shin
- Gait: Wide-based, ataxic, positive Romberg
- Musculoskeletal: High-arched feet (pes cavus); hammer toes; thoracolumbar scoliosis
Workup:
- MRI brain and spine: Mild cerebellar atrophy; cervical cord atrophy
- Genetic testing: Homozygous GAA trinucleotide repeat expansion in FXN gene (frataxin) - 850 repeats (normal <33)
- Echocardiogram: Concentric left ventricular hypertrophy (hypertrophic cardiomyopathy)
- ECG: T-wave inversions
- Glucose tolerance test: Impaired glucose tolerance
- Nerve conduction studies: Absent sensory responses (sensory neuronopathy); motor studies relatively preserved
Diagnosis: Friedreich ataxia
Treatment:
- No disease-modifying therapy currently available (clinical trials ongoing)
- Cardiology follow-up for hypertrophic cardiomyopathy management
- Idebenone (antioxidant) considered for potential cardiac benefit
- Physical and occupational therapy
- Speech therapy for dysarthria
- Orthopedic evaluation for scoliosis and foot deformities
- Diabetes screening annually
- Genetic counseling for family (autosomal recessive inheritance)
- Progressive wheelchair dependence anticipated within 10-15 years
Clinical Pearl: Friedreich ataxia is the most common inherited ataxia, caused by GAA repeat expansion in the FXN gene encoding frataxin, a mitochondrial protein involved in iron-sulfur cluster assembly. The combination of cerebellar ataxia with ABSENT reflexes (areflexia) is the key clinical clue - most cerebellar disorders cause hyperreflexia, but Friedreich involves the peripheral sensory neurons (dorsal root ganglia) as well, causing a sensory neuropathy. Additional features include cardiomyopathy (the leading cause of death), diabetes, scoliosis, and pes cavus. Age of onset before 25 and areflexia are diagnostic requirements. The sensory ataxia (posterior column involvement) compounds the cerebellar ataxia.