Mitochondrial cytopathy presenting with cerebellar ataxia

A previously fit and well 59 year old man presented with a 3 year history of slowly progressive decline in mobility with increasing unsteadiness and falls. He also reported clumsiness of both hands and his wife noted poor memory. There was no family history of note, including deafness and diabetes. He drank alcohol occasionally. On examination he had signs consistent with a cerebellar and pyramidal syndrome with subcortical cognitive impairment.

An MRI scan of the brain and spine showed significant generalised cerebral atrophy. CSF protein was 0.80g/L, with normal cell count and no oligoclonal bands. Blood tests were normal or negative for antineuronal antibodies, vitamin E, coeliac disease, autoimmune screen. Genetic tests for spinocerebellar ataxias, Freidreich's, fragile X syndrome and DRPLA were also negative. Muscle biopsy revealed mitochondrial aggregation with COX negative fibres, in keeping with a mitochondrial disorder. Genetic testing found a novel mtDNA variant (p.GLY46Asp) at low levels within the MT-CO3 gene.

He has subsequently developed myoclonus and generalised tonic clonic seizures but there is no evidence of other system involvement.

Mitochondrial disorders should be considered in the differential diagnosis of cerebellar ataxia, even in the absence of multisystem involvement or a significant family history.