SPG3A -linked hereditary spastic paraplegia associated with cerebral glucose hypometabolism
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CASE REPORT
SPG3A-linked hereditary spastic paraplegia associated with cerebral glucose hypometabolism Tatsuhiro Terada • Satoshi Kono • Yasuomi Ouchi Kenichi Yoshida • Yasushi Hamaya • Shigeru Kanaoka • Hiroaki Miyajima
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Received: 21 August 2012 / Accepted: 27 November 2012 / Published online: 12 December 2012 Ó The Japanese Society of Nuclear Medicine 2012
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 [18F]-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 T. Terada S. Kono (&) H. Miyajima First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan e-mail: [email protected] T. Terada Y. Ouchi Laboratory of Human Brain Imaging Research, Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan K. Yoshida Y. Hamaya S. Kanaoka Department of Molecular Diagnosis, Hamamatsu University School of Medicine, Hamamatsu, Japan
in the SPG3A gene may be present more centrally than previously assumed. Keywords PET SPG3A Atlastin Frontal Assessment Battery
Introduction Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by slowly progressive spasticity and weakness of the lower limbs [1, 2]. A traditional classification has distinguished between two major phenotypes based on the presence (complicated form of HSP) or absence (pure form of HSP) of accompanying clinical features including ataxia, amyotrophy, optic atrophy, pigmentary retinopathy, mental retardation, extrapyramidal sighs, dementia, peripheral neuropathy and epilepsy [1, 2]. SPG3A-linked hereditary spastic paraplegia is caused by a mutation in the SPG3A gene, which encodes a GTPase called atlastin [3]. Mutations in the SPG3A gene have been reported to be responsible for *10 % of autosomal dominant HSP [4]. The phenotyp
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