Clinical, imaging, and neuropathological characterization of multiple system degeneration associated with a novel SERAC1 variant in a mixed-breed dog.

A novel SERAC1 variant was identified as a genetic cause of progressive multiple system neurodegeneration in a dog.

A 7-month-old spayed female mixed-breed dog presented with a subacute, progressive cerebellar syndrome characterized by ataxia and intention tremors. Initial brain MRI demonstrated moderate cerebellar atrophy and mild bilateral symmetrical intra-axial lesions within the caudate nuclei, raising suspicion for a neurodegenerative disorder. Over a 2-year follow-up period, the neurological signs worsened, including suspected myoclonic epileptic seizures and severe cerebellar ataxia. Repeat MRI confirmed progressive cerebellar and cerebral atrophy with well-defined, bilateral, symmetrical caudate nuclei lesions. Post-mortem histopathology revealed severe cerebellar degeneration with loss of Purkinje cells and depletion of both the granular and molecular layers, as well as malacic areas in the caudate nuclei characterized by extensive necrosis. Genetic testing identified a novel candidate variant in the SERAC1 gene on chromosome 1. SERAC1 encodes a phosphatidylglycerol remodeling enzyme critical for mitochondrial function and intracellular cholesterol trafficking. This variant is consistent with a diagnosis of multiple system degeneration, a rare inherited neurodegenerative condition in dogs that phenotypically resembles MEGD(H)EL syndrome in humans — characterized by 3-methylglutaconic aciduria, deafness-dystonia, hepatopathy, encephalopathy, and Leigh-like syndrome. This case expands the understanding of canine neurogenetic diseases and highlights SERAC1 as a candidate gene for progressive neurodegenerative disorders in dogs, supporting the value of genetic screening in young dogs with unexplained progressive cerebellar disease.

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