TY - JOUR
T1 - Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature
AU - Cioffi, Ettore
AU - Coppola, Gianluca
AU - Musumeci, Olimpia
AU - Gallone, Salvatore
AU - Silvestri, Gabriella
AU - Rossi, Salvatore
AU - Piemonte, Fiorella
AU - D’Amico, Jessica
AU - Tessa, Alessandra
AU - Santorelli, Filippo Maria
AU - Casali, Carlo
PY - 2024
Y1 - 2024
N2 - Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG46 is a rare, early-onset and autosomal recessive HSP, linked to biallelic GBA2 mutations. About thirty families have been described worldwide, with different phenotypes like complicated HSP, recessive cerebellar ataxia or Marinesco-Sjogren Syndrome. Herein, we report five SPG46 patients harbouring five novel GBA2 mutations, the largest series described in Italy so far. Probands were enrolled in five different centres and underwent neurological examination, clinical cognitive assessment, column imaging for scoliosis assessment, ophthalmologic examination, brain imaging, GBA2 activity in peripheral blood cells and genetic testing. Their phenotype was consistent with HSP, with notable features like upper gaze palsy and movement disorders. We review demographic, genetic, biochemical and clinical information from all documented cases in the existing literature, focusing on the global distribution of cases, the features of the syndrome, its variable presentation, new potential identifying features and the significance of measuring GBA2 enzyme activity.
AB - Hereditary spastic paraparesis (HSP) is a group of central nervous system diseases primarily affecting the spinal upper motor neurons, with different inheritance patterns and phenotypes. SPG46 is a rare, early-onset and autosomal recessive HSP, linked to biallelic GBA2 mutations. About thirty families have been described worldwide, with different phenotypes like complicated HSP, recessive cerebellar ataxia or Marinesco-Sjogren Syndrome. Herein, we report five SPG46 patients harbouring five novel GBA2 mutations, the largest series described in Italy so far. Probands were enrolled in five different centres and underwent neurological examination, clinical cognitive assessment, column imaging for scoliosis assessment, ophthalmologic examination, brain imaging, GBA2 activity in peripheral blood cells and genetic testing. Their phenotype was consistent with HSP, with notable features like upper gaze palsy and movement disorders. We review demographic, genetic, biochemical and clinical information from all documented cases in the existing literature, focusing on the global distribution of cases, the features of the syndrome, its variable presentation, new potential identifying features and the significance of measuring GBA2 enzyme activity.
KW - Hereditary spastic paraparesis
KW - Literature review
KW - Non-lysosomal glucosylceramidase
KW - Hereditary spastic paraparesis
KW - Literature review
KW - Non-lysosomal glucosylceramidase
UR - http://hdl.handle.net/10807/267054
U2 - 10.1007/s10048-024-00749-9
DO - 10.1007/s10048-024-00749-9
M3 - Article
SN - 1364-6745
SP - N/A-N/A
JO - Neurogenetics
JF - Neurogenetics
ER -