Gaucher disease ascertained through a Parkinson's center: imaging and clinical characterization.
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.
Saunders-Pullman
Rachel
R
Department of Neurology, Beth Israel Medical Center, New York, New York 10003, USA. rsaunder@bethisraelny.org
Hagenah
Johann
J
Dhawan
Vijay
V
Stanley
Kaili
K
Pastores
Gregory
G
Sathe
Swati
S
Tagliati
Michele
M
Condefer
Kelly
K
Palmese
Christina
C
Brüggemann
Norbert
N
Klein
Christine
C
Roe
Am
A
Kornreich
Ruth
R
Ozelius
Laurie
L
Bressman
Susan
S
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
D019788:Fluorodeoxyglucose F18; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D005962:Glucosylceramidase