Very late onset Friedreich ataxia: a case report

Friedreich ataxia (FRDA) is a rare autosomal recessive hereditary disorder caused by expansion of a GAA repeats in the first intron of the X25 gene. It typically begins before the age of 25, but up to 25% of patients may be considered atypical with respect to the established diagnostic criteria, showing delayed age at onset with mild clinical impairment, slower progression of disease, and fewer secondary complications. These patients are arbitrarily subdivided into late-onset FRDA [LOFA; 25-39 years] and very late-onset FRDA [VLOFA; ≥40 years], show retained deep tendon reflexes and unusually gradual disease progression. Here we describe a 63-year-old white woman showing lower limb spasticity with ataxia and preserved ankle and knee jerks. The progression was slowly during the past 6 years, family history was negative for neurological diseases and no consanguinity was reported. Cerebellar dysartria, axonal neuropathy and reduced glucose tolerance were also present. Brain NMR showed cerebellar and cortical atrophy. Molecular analysis revealed a pathologic GAA expansion in the gene encoding frataxin, carrying expanded alleles in the low-range size, corresponding to 110 and 180 GAA repeats. VLOFA is an infrequent subtype of the disease with onset ranging between 40 and 67 years. Nevertheless, considering the frequency of FRDA mutations carriers in the general population (1/60), and the associated risk of recurrence, this condition deserve to be considered in atypical ataxic patients, even when the full clinical criteria for a classical form are not satisfied.