Friedreich ataxia
Epidemiology
- The most common autosomal recessive ataxia
- Peak incidence: 8–15 years (most cases < 25 years)
Etiology
- 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
Pathophysiology
Clinical features
Mnemonic
Friedreich is fratastic (frataxin): he’s your favorite frat brother, always staggering and falling but has a sweet, big heart. Ataxic GAAit.
- Neurological
- Progressive ataxia (impaired coordination of muscles) of all limbs due to damage to the spinocerebellar tracts (often a presenting feature)
- Both sensory and cerebellar features
- Associated symptoms
- Impaired proprioception and vibration sense (pallhypesthesia) due to damage to the dorsal columns
- Loss of deep tendon reflexes due to degeneration of the dorsal root ganglia
- Spastic paralysis due to degeneration of the lateral corticospinal tract
- Nystagmus
- Dysarthria and dysphagia (may be accompanied by uncoordinated breathing)
- Progressive ataxia (impaired coordination of muscles) of all limbs due to damage to the spinocerebellar tracts (often a presenting feature)
- Skeletal deformities
- Secondary scoliosis (kyphoscoliosis): usually occurs in childhood
- Due to decreased muscle tone and muscle atrophy, which leave the spinal column unsupported.
- Foot deformity: foot inversion (talipes equinovarus) and/or high-arched foot (pes cavus) with hammer toes
- Thought to be a result of paretic small foot muscles.
- Secondary scoliosis (kyphoscoliosis): usually occurs in childhood
- Other features
- Concentric hypertrophic cardiomyopathy: palpitations, arrhythmias, dyspnea, exercise intolerance
- Diabetes mellitus
- Personality changes (e.g., emotional lability)
Diagnostics
Mimics Vitamin E deficiency