title: SPG3A-linked hereditary spastic paraplegia associated with cerebral glucose hypometabolism.
abstract: SPG3A-linked hereditary spastic paraplegia (HSP) is a rare autosomal dominant motor disorder caused by a mutation in the SPG3A gene, and is characterized by progressive motor weakness and spasticity in the lower limbs, without any other neurological abnormalities. SPG3A-linked HSP caused by a R239C mutation has been reported to present a pure phenotype confined to impairment of the corticospinal tract. However, there is still a debate about the etiology of this motor deficit with regard to whether it is peripheral or central. We herein report two patients who were heterozygous for a R239C mutation in the SPG3A gene. Two middle-aged Japanese sisters had been suffering from a pure phenotype of HSP since their childhood. Both patients had a significant decrease in glucose metabolism in the frontal cortex medially and dorsolaterally in a [(18)F]-fluorodeoxyglucose (FDG) positron emission photography (PET) study and low scores on the Frontal Assessment Battery. A real-time PCR analysis in normal subjects showed the frontal cortex to be the major location where SPG3A mRNA is expressed. The present finding that the frontal glucose hypometabolism was associated with frontal cognitive impairment indicates that widespread neuropathology associated with mutations in the SPG3A gene may be present more centrally than previously assumed.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Terada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kono
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hamaya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanaoka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
mesh_terms: D002648:Child; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics*; D005947:Glucose / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D015419:Spastic Paraplegia, Hereditary / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D019204:GTP-Binding Proteins; D005947:Glucose