Progressive myoclonic ataxia due to late-onset sialidosis

A 70-year-old woman presented with slowly progressive mobility difficulty and involuntary jerking movements, which had started at age 55 years. On examination, she had generalised action-induced myoclonus and gait ataxia. Extensive investigation over 10 years had not given a diagnosis. Genetic testing was re-visited and she was found to carry a likely pathogenic variant and a variant of unknown significance in the neuraminidase gene. Dermal fibroblast culture identified significantly reduced neuraminidase activity in keeping with a diagnosis of late-onset sialidosis. Taking into account biochemical evidence and the clinical phenotype, the identified variants have been reclassified as pathogenic and likely pathogenic. This case shows the value in revisiting genetic testing in unresolved cases and the need to be aware of the presentation of inherited rare metabolic disorders in later life.