Spinal cord-predominant neuropathology in an adult-onset case of POLR3A-related spastic ataxia.
Trevor M SytsmaDong-Hui ChenBradley RolfMichael DorschnerSuman JayadevC Dirk KeeneJing ZhangThomas D BirdCaitlin S LatimerPublished in: Neuropathology : official journal of the Japanese Society of Neuropathology (2021)
Biallelic mutations in POLR3A have been associated with childhood-onset hypomyelinating leukodystrophies and adolescent-to-adult-onset spastic ataxia, the latter of which has been linked to the intronic variant c.1909 + 22G>A. We report a case of adult-onset spastic ataxia in a 75-year-old man, being a compound heterozygous carrier of this variant, whose brain and spinal cord were for the first time investigated by neuropathological examination. We describe prominent degeneration of the posterior columns, spinocerebellar tracts, and anterior corticospinal tracts of the spinal cord in a pattern resembling Friedreich's ataxia, with a notable lack of significant white matter pathology throughout the brain, in marked contrast with childhood-onset cases. Immunohistochemical examination for the POLR3A protein demonstrated no apparent differences in localization or staining intensity between the proband and an age-matched control subject. We demonstrate the clinicopathologic description of POLR3A-related neurodegenerative disease and also mention the differential diagnosis of the childhood-onset hypomyelinating leukodystrophy and late-onset spastic ataxia phenotypes.
Keyphrases
- early onset
- spinal cord
- late onset
- white matter
- cerebral palsy
- botulinum toxin
- neuropathic pain
- spinal cord injury
- upper limb
- childhood cancer
- early life
- young adults
- multiple sclerosis
- resting state
- mental health
- magnetic resonance
- intellectual disability
- magnetic resonance imaging
- mass spectrometry
- small molecule
- computed tomography
- atomic force microscopy
- contrast enhanced
- drug induced
- single molecule
- transcranial magnetic stimulation
- subarachnoid hemorrhage
- cerebral ischemia