Genetic Ataxias: querying a lifelong diagnosis


Antonia Ross, Dr Richard Chatoor, Dr Taylor Scott, Professor Paul Finucane

Background

Friedreich ataxia is a rare autosomal recessive disease within the group of hereditary ataxias. It is commonly caused by a mutation of the frataxin encoding gene, which results in the repeat expansion of GAA trinucleotide repeat within chromosome 9q13. Clinical manifestations of the disease depend upon the number of GAA expansions and interruptions by non-GAA repeats, as well as the size of each GAA expansion. In contrast, Spinocerebellar ataxia is an autosomal dominant cause of hereditary ataxia. Spinocerebellar ataxia commonly involves a repeat expansion mutation of the CAG encoding gene, with over 30 recognised variants of the disease.

Case

We report the case of a 72-year-old female resident of a high-level care nursing home who demonstrated clinical signs of global incoordination (dysarthria, bilateral dysdiadochokinesia, bilateral dysmetria), nystagmus, pronator drift, reduced tone, power and reflexes of the upper and lower limbs, as well as pes cavus and scoliosis. The onset of incoordination occurred at the age of 21 years and resulted in a purported diagnosed of Friedreich ataxia, without confirmatory genetic testing.

During her recent admission, the historical diagnosis of Friedreich ataxia was queried due to the relatively late presentation of the patient’s symptoms, as well as her advanced age and ongoing functional capacity. The patient’s family pedigree identified five additional family members affected by similar physical disabilities and four with possible diagnoses of Spinocerebellar ataxia, but also without confirmatory genetic testing.

A CT brain demonstrated findings consistent with cerebellar atrophy and both Frataxin and Spinocerebellar gene screens were conducted in an attempt to confirm the underlying cause of her ataxia. The Frataxin screening test indicated that our patient is unlikely to be affected by Friedreich ataxia due to a low number of GAA nucleotide repeats. The Spinocerebellar gene screen is still pending and is hoped to provide diagnostic certainty for the patient. We anticipate that a positive Spinocerebellar test result will have far-reaching implications for our patient’s relatives who could be carriers or affected individuals. Nevertheless, we recognise the limits of genetic testing and acknowledge that a definitive diagnosis is often unable to be provided to patients affected by hereditary ataxias.