title: Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease.
abstract: Mutations in the glucocerebrosidase (GBA1) gene, the most common genetic contributor to Parkinson's disease (PD), are associated with an increased risk of PD in heterozygous and homozygous carriers. While glucocerebrosidase enzyme (GCase) activity is consistently low in Gaucher disease, there is a range of leukocyte GCase activity in healthy heterozygous GBA1 mutation carriers. To determine whether GCase activity may be a marker for PD with heterozygous GBA1 mutations (GBA1 mutation PD, GBA PD), GBA PD patients (n=15) were compared to PD patients without heterozygous GBA1 mutations (idiopathic PD; n=8), heterozygous GBA1 carriers without PD (asymptomatic carriers; n=4), and biallelic mutation carriers with PD (Gaucher disease with PD, GD1 PD; n=3) in a pilot study. GCase activity (nmol/mg protein/hour) in GD1 PD (median [interquartile range]; minimum-maximum: 6.4 [5.7]; 5.3-11) was lower than that of GBA PD (16.0 [7.0]; 11-40) (p=0.01), while GCase activity in GBA PD was lower than idiopathic PD (28.5 [15.0]; 16-56) (p=0.01) and asymptomatic carriers (25.5 [2.5]; 23-27) (p=0.04). Therefore, GCase activity appears to be a possible marker of heterozygous GBA1 mutation PD, and larger studies are warranted. Prospective studies are also necessary to determine whether lower GCase activity precedes development of PD.
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Roberto A
authors: RA
authors: Ortega
authors: Department of Neurology, NYU Langone Medical Center, New York, NY, USA.
authors: Paola A
authors: PA
authors: Torres
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Matthew
authors: M
authors: Swan
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, OH, USA.
authors: William
authors: W
authors: Nichols
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Sarah
authors: S
authors: Boschung
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Deborah
authors: D
authors: Raymond
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Matthew J
authors: MJ
authors: Barrett
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Brooke A
authors: BA
authors: Johannes
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Lawrence
authors: L
authors: Severt
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Vicki
authors: V
authors: Shanker
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA.
authors: Ann L
authors: AL
authors: Hunt
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA; Department of Neurology, Mount Sinai School of Medicine, NY, USA.
authors: Susan
authors: S
authors: Bressman
authors: Department of Neurology, NYU Langone Medical Center, New York, NY, USA; Mater Misericordiae University Hospital, Dublin, Ireland.
authors: Gregory M
authors: GM
authors: Pastores
authors: Department of Neurology, Mount Sinai Beth Israel Medical Center, 10 Union Square East, Suite 5J, New York, NY 10003, USA; Department of Neurology, Mount Sinai School of Medicine, NY, USA. Electronic address: rsaunder@bethisraelny.org.
authors: Rachel
authors: R
authors: Saunders-Pullman
mesh_terms: D000368:Aged; D005260:Female; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*
chemical_list: D005962:Glucosylceramidase
keywords: Biomarker; GBA; GBA enzyme activity; Gaucher; Glucocerebrosidase; Parkinson’s disease