title: Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier.
abstract: A clinical association between Gaucher disease and parkinsonism has been demonstrated. We herein report a Japanese patient with type 3 Gaucher disease who was compound heterozygous for F213I and L444P mutations in the glucocerebrosidase gene while his father was heterozygous for the L444P mutation. They both presented with parkinsonism characterized by a predominance of akinetic-rigid signs and a favorable response to anti-Parkinson therapies. We investigated the dopaminergic neuronal function using positron emission tomography (PET) with radioligands, [(11)C] CFT and [(11)C] raclopride. PET studies of both patients demonstrated the [(11)C] CFT uptake to be severely decreased in the putamen and the caudate nucleus, however, the [(11)C] raclopride uptake was normal in the basal ganglia. Although the majority of Gaucher disease patients with parkinsonism tend to be refractory to anti-Parkinson therapies. The clinical features and the findings of the PET studies suggest that patients with parkinsonism associated with the mutation in the glucocerebrosidase gene, even in heterozygosis, may be related to the presynaptic dopaminergic neuronal dysfunction reported in Parkinson's disease. A PET study to evaluate the dopaminergic neuronal function in Gaucher disease would provide both a better understanding of the effects of anti-Parkinson therapies and a help to improve our ability to make an early diagnosis of parkinsonism associated with Gaucher disease.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. satokono@hama-med.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kono
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shirakawa
authors.forename: Yasuomi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugiura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D003042:Cocaine / Q000031:analogs & derivatives; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D005776:Gaucher Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D049268:Positron-Emission Tomography; D020891:Raclopride
chemical_list: D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D020891:Raclopride; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D004298:Dopamine