Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class

. he hereditary spastic paraplegias (HSPs) are a group of single gene disorders in which the corticospinal tracts fail to develop normally, or degenerate after initially normal development. The HSPs all share the principal clinical feature of progressive lower limb spastic paralysis, and are subdivided into pure and complicated forms, depending on the presence of additional neurological or non-neurological features. 12 The pure HSPs tend to be associated with neurodegeneration, rather than abnormal development, and histopathological studies in pure HSP show a length-dependent ‘‘dying back’’ of the terminal ends of the corticospinal tract axons, with the longest axons being involved first. 1 The SPG4 gene, spastin, is the most important pure HSP gene, being responsible for approximately 40% of definite autosomal dominant pure HSP and a smaller proportion of sporadic cases and cases with uncertain family history. 34 The 616 amino acid spastin protein is a widely expressed AAA (ATPases associated with diverse cellular activities) protein. 5