Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurological 
disorders characterized primarily by a pyramidal syndrome with lower limb 
spasticity, which can manifest as pure HSP or associated with a number of 
neurological or non-neurological signs (i.e., complicated HSPs). The clinical 
variability of HSPs is associated with a wide genetic heterogeneity, with more 
than eighty causative genes known. Recently, next generation sequencing (NGS) 
has allowed increasing genetic definition in such a heterogeneous group of 
disorders. We report on a 56- year-old man affected by sporadic complicated HSP 
consisting of a pyramidal syndrome, cerebellar ataxia, congenital cataract, pes 
cavus, axonal sensory-motor peripheral neuropathy and cognitive decline. Brain 
MRI showed cerebellar atrophy and thin corpus callosum. By NGS we found a novel 
homozygous biallelic c.452-1G > C mutation in the b-glucosidase 2 gene (GBA2), 
known to be causative for autosomal recessive hereditary spastic paraplegia type 
46 (SPG46). The rarity of this inherited form besides reporting on a novel 
mutation, expands the genetic and clinical spectrum of SPG46 related HSP.