- Clinical science
Friedreich ataxia (FDRA) is an autosomal recessive disorder involving trinucleotide repeat expansion that leads to progressive neurodegeneration. It affects multiple spinal cord tracts, causing muscle weakness and impaired coordination of all limbs. A staggering gait in childhood is the resulting main symptom. Other features include skeletal abnormalities, cardiomyopathy, and diabetes. The clinical course is mainly determined by the extent of the loss of mobility and cardiac involvement. Diagnosis requires confirmation with genetic tests. Because there is no curative therapy available, the prognosis is poor.
- Trinucleotide repeat expansion (of the nucleotide triplet GAA) in the FXN gene on chromosome 9 → deficiency of frataxin (an iron-binding protein) → intramitochondrial accumulation of iron and dysregulation of cellular antioxidant defense; due to mitochondrial dysfunction → oxidative damage and degeneration of CNS and PNS
Progressive ataxia (impaired coordination of muscles) of all limbs due to damage to the spinocerebellar tracts (often a presenting feature)
- Bilateral lower limbs equally affected
- Wide-based gait with frequent falling
- Titubation while standing or sitting
- Arms: action and intention tremors
- Associated symptoms
- Gait ataxia
- Spastic paralysis due to degeneration of the lateral corticospinal tract
- Dysarthria and dysphagia (may be accompanied by uncoordinated breathing)
- Bladder dysfunction
- Hearing loss
- Progressive ataxia (impaired coordination of muscles) of all limbs due to damage to the spinocerebellar tracts (often a presenting feature)
- Skeletal deformities
- Other features
Individuals with FRiedreich ATAXia have ATAXic GAAit due to the expansion of the triplet GAA in the FRATAXin gene.
- A specific trinucleotide repeat expansion assay should be performed in all suspected cases.
- ECG: T-wave inversion and ventricular hypertrophy
- Echocardiography: symmetric, concentric ventricular hypertrophy
Nerve conduction studies
- Sensory: absent or reduced sensory nerve action potentials (SNAP)
- Motor: normal until advanced stages
- MRI brain and spinal cord: cervical spine atrophy (minimal cerebellar atrophy)
- Carrier testing of relatives
- Prenatal testing: Genetic counseling is recommended for parents with one affected child.