An autopsy case of adult-onset hereditary spastic paraplegia type 2 with a novel mutation in exon 7 of the proteolipid protein 1 gene

We report an autopsy case of rare adult-onset spastic paraplegia type 2 (SPG2) with a novel missense mutation in exon 7 of the proteolipid protein 1 gene (PLP1). The patient was a 67-year-old man whose elder brother had died of a similar disease with onset in his 40s. Thirty-three years before death at the age of 35, he noticed difficulty in walking. He gradually became abasic over a period of 6 years. He also developed progressive dementia and eventually became bed-ridden by 28 years after onset. At autopsy, gross inspection revealed diffuse, moderate atrophy of the cerebrum with a dilated ventricular system and softening of the white matter throughout the central nervous system (CNS). Histopathologically, the CNS showed widespread myelin pallor in the white matter. By contrast, the gray matter and peripheral nerves were well preserved. Some white matter tracts, including the corticospinal tracts, were preferentially affected, and severe axonal degeneration was observed in these tracts. Genetic analysis revealed a novel mutation, p.Tyr263Cys, in exon 7 of PLP1. This case represents an adult-onset SPG2 patient with one of the oldest ages of onset reported to date. The late onset and long clinical course suggest that this novel mutation does not affect the maturation of oligodendrocytes, but is related to insufficient maintenance of myelin.