Clinical, imaging, and neuropathological characterization of multiple system degeneration associated with a novel...

A 7-month-old spayed female mixed-breed dog was evaluated for a subacute, progressive, cerebellar syndrome characterized by ataxia and intention tremors. Brain magnetic resonance imaging (MRI) revealed moderate cerebellar atrophy and mild bilateral symmetrical intra-axial lesions at the level of the caudate nuclei. A neurodegenerative disorder was suspected. Over a 2-year period, signs of neurologic disease worsened with suspected myoclonic epileptic seizures and severe cerebellar ataxia. Follow-up MRI showed progressive cerebellar and cerebral atrophy, as well as well-defined, bilateral, and symmetrical lesions affecting the caudate nuclei. Histopathology revealed severe cerebellar degeneration with a loss of Purkinje cells and depletion of the granular and molecular layers. Malacic areas at the level of the caudate nuclei characterized by extensive necrosis were observed. Genetic testing identified a clear top candidate variant in the SERAC1 gene on chromosome 1. These findings are consistent with multiple system degeneration, a rare inherited neurodegenerative disorder resembling MEGD(H)EL syndrome (3-methylglutaconic aciduria with deafness-dystonia, [hepatopathy], encephalopathy, and Leigh-like syndrome) in humans.