Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature.
Ettore CioffiGianluca CoppolaOlimpia MusumeciSalvatore GalloneGabriella SilvestriSalvatore RossiFiorella PiemonteJessica D'AmicoAlessandra TessaFilippo Maria SantorelliCarlo CasaliPublished in: Neurogenetics (2024)
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-Sjögren 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.
Keyphrases
- early onset
- heat shock protein
- heat shock
- heat stress
- peripheral blood
- intellectual disability
- late onset
- high resolution
- end stage renal disease
- spinal cord
- case report
- cerebral palsy
- ejection fraction
- copy number
- chronic kidney disease
- newly diagnosed
- induced apoptosis
- systematic review
- prognostic factors
- mitochondrial dna
- upper limb
- autism spectrum disorder
- botulinum toxin
- gene expression
- cerebrospinal fluid
- liquid chromatography
- dna methylation
- muscular dystrophy
- multiple sclerosis
- cerebral ischemia
- blood brain barrier
- patient reported outcomes
- cell proliferation
- white matter
- climate change
- disease activity
- cell death
- human health