Spastic paraplegia type 46: novel and recurrent GBA2 gene variants in a compound heterozygous Italian patient with spastic ataxia phenotype

Neurol Sci. 2021 Jul 12. doi: 10.1007/s10072-021-05463-0. Online ahead of print.


Introduction: Spastic paraplegia type 46 (SPG46) is a rare autosomal recessive hereditary spastic paraplegia, caused by mutations in the non-lysosomal glucosylceramidase β2 (GBA2) gene. Worldwide, approximately twenty SPG46 families have been identified so far.

Case report: We describe a compound heterozygous Italian patient carrying a novel (p.Arg879Gln) and a recurrent (p.Arg399 *) GBA2 gene variant. The patient presented unsteady gait at age 2, and progressively manifested spastic-ataxia, scoliosis, mild intellectual decline, and bilateral cataract.

Discussion: Clinical manifestations associated with GBA2 gene variants encompass a spectrum of overlapping phenotypes including cerebellar ataxia, spastic paraplegia, and Marinesco-Sjogren-like syndrome. We review previously reported cases of SPG46 and discuss possible genetic differential diagnosis.

Keywords: GBA2; Hereditary spastic paraplegia; Spastic ataxia.