Ataxia in children: Case

This boy has Friedreich ataxia. The cardinal constellation is a progressive limb and gait ataxia over two years in a teenager, with scanning speech and clumsiness of the hands, absent knee and ankle reflexes, extensor plantar responses, loss of position and vibration sense in the lower limbs, bilateral pes cavus, a thoracic scoliosis, and a hypertrophic cardiomyopathy on the echocardiogram. The onset is in adolescence and before twenty-five, and the combination of absent lower limb reflexes with an extensor plantar response and dorsal column loss is the signature that separates Friedreich ataxia from a pure cerebellar lesion. The diagnosis is confirmed by the targeted genetic test for the GAA trinucleotide repeat expansion in the FXN gene, and the condition is the most common inherited ataxia in populations of European descent, inherited in an autosomal recessive pattern.

Confirming the diagnosis and the mechanism

The clinical picture alone makes the diagnosis highly probable, and the confirmatory test is the genetic test for the GAA trinucleotide repeat expansion in the FXN gene on chromosome nine. Friedreich ataxia is autosomal recessive, and the GAA repeat expansion reduces the production of frataxin, a mitochondrial protein that assembles iron-sulphur clusters for the electron transport chain. The loss of frataxin starves the metabolically demanding neurons of the dorsal root ganglia and the dorsal columns, and the cardiomyocytes of the heart, which is the single mechanism that produces the sensory ataxia, the loss of position and vibration sense, the cardiomyopathy, and the diabetes. I would arrange the FXN genetic test as the first and definitive investigation, and I would perform a magnetic resonance imaging to document the cerebellar and spinal cord involvement and to exclude a structural lesion, though the genetic test is the diagnostic anchor. ^[5]