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Spinal cord‐predominant neuropathology in an adult‐onset case of POLR3A ‐related spastic ataxia
Author(s) -
Sytsma Trevor M.,
Chen DongHui,
Rolf Bradley,
Dorschner Michael,
Jayadev Suman,
Keene C. Dirk,
Zhang Jing,
Bird Thomas D.,
Latimer Caitlin S.
Publication year - 2022
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12775
Subject(s) - neuropathology , ataxia , medicine , spastic , physical medicine and rehabilitation , psychiatry , cerebral palsy , disease
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.