title: Gaucher disease ascertained through a Parkinson's center: imaging and clinical characterization.
abstract: Among the genes implicated for parkinsonism is glucocerebrosidase (GBA), which causes Gaucher disease (GD). Despite a growing literature that GD may present as parkinsonism, neuroimaging, olfaction, and neuropsychological testing have not been extensively reported. We describe transcranial sonography (TCS), 18F-fluorodopa (F-dopa) and fluorodeoxyglucose (FDG) Positron emission tomography, olfaction testing, neuropsychological testing, and clinical features in homozygous and compound heterozygous GBA mutation carriers identified through screening of 250 Ashkenazi Jewish parkinsonian individuals treated at a tertiary care center. We identified two individuals with N370S/R496H compound heterozygous mutations and two with N370S homozygous mutations; one individual died before completing detailed evaluation. TCS (n = 3) demonstrated nigral hyperechogenicity that was greater than controls [median area maximal substantia nigra echogenicity (aSNmax) = 0.28 cm(2) vs. 0.14 cm(2), P = 0.005], but similar to idiopathic PD (aSNmax = 0.31 cm(2)). FDG PET (n = 2) demonstrated hypermetabolism of the lentiform nuclei, and F-fluorodopa PET (n = 2), bilateral reduction in striatal F-dopa uptake. Olfaction was markedly impaired in the two tested cases, including onset of smell disturbance in adolescence in one. Neuropsychological features (n = 3) were consistent with Parkinson's disease (PD) or diffuse Lewy body disease (DLB). The imaging, neuropsychological and olfactory markers suggest the GD phenotype includes PD with and without features of DLB, marked olfactory loss, nigral hyperechogenicity on TCS, and F-dopa and FDG PET abnormalities.
authors.affiliation: Department of Neurology, Beth Israel Medical Center, New York, New York 10003, USA. rsaunder@bethisraelny.org
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Vijay
authors.initials: V
authors.lastname: Dhawan
authors.forename: Kaili
authors.initials: K
authors.lastname: Stanley
authors.forename: Gregory
authors.initials: G
authors.lastname: Pastores
authors.forename: Swati
authors.initials: S
authors.lastname: Sathe
authors.forename: Michele
authors.initials: M
authors.lastname: Tagliati
authors.forename: Kelly
authors.initials: K
authors.lastname: Condefer
authors.forename: Christina
authors.initials: C
authors.lastname: Palmese
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Am
authors.initials: A
authors.lastname: Roe
authors.forename: Ruth
authors.initials: R
authors.lastname: Kornreich
authors.forename: Laurie
authors.initials: L
authors.lastname: Ozelius
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
mesh_terms: D000328:Adult; D000368:Aged; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D005260:Female; D019788:Fluorodeoxyglucose F18; D005776:Gaucher Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D000857:Olfaction Disorders / Q000209:etiology; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis*; D010641:Phenotype; D049268:Positron-Emission Tomography / Q000379:methods; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods
chemical_list: D019788:Fluorodeoxyglucose F18; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D005962:Glucosylceramidase