None of the authors have financial or other considerations which may have impacted the results reported in this study

None of the authors have financial or other considerations which may have impacted the results reported in this study

• None of the authors have financial or other considerations which may have impacted the results reported in this study

1990: Israel: Dr. Aghai asked about a possible association between Gaucher disease and Parkinson disease

• 1990: Israel: Dr. Aghai asked about a possible association between Gaucher disease and Parkinson disease

• 1993: Italy: Prof. Bembi introduces the “oldest patient with type 3 Gaucher disease” because she had Parkinson disease

• 1994: Jerusalem: Presentation of a Gaucher patient with severe Parkinson disease, refractory to L-DOPA

• 1996: First publication of 6 Gaucher patients with parkinsonism: common features = mild Gaucher and severe, early-onset Parkinson disease, refractory to L-DOPA

150 DNA samples of patients with Parkinson

• 150 DNA samples of patients with Parkinson

• disease from 5 Israeli centers

• Mutation analysis limited to N370S

• 94 (62%) males and 56 (38%) females

• No Parkinson patient had Gaucher disease or had a family history of Gaucher disease

• Mean age 71.3 years (range: 42-90)

• Mean age PD diagnosis: 65.6 years (range: 34-84) years

• PD characterized by Hoen & Yahr scale

16 (10.6%) patients with PD were carriers of N370S

• 16 (10.6%) patients with PD were carriers of N370S

• One patient (0.6%) was homozygous

• Carrier rate not statistically significant

• Mean age PD onset in carriers: 57.0 (±11.1) years versus 66.8 (±9.7) years among non-carriers (p=0.003)

• No statistically significant difference in Hoen &Yahr severity scale between carriers and non-carriers

99 Ashkenazi Jewish Israeli patients with idiopathic Parkinson disease

• 99 Ashkenazi Jewish Israeli patients with idiopathic Parkinson disease

• Screened for six Gaucher mutations: N370S, L444P, 84GG, IVS+1, V394L, and R496H

99 Ashkenazi Jewish Israeli patients with idiopathic Parkinson disease

• 99 Ashkenazi Jewish Israeli patients with idiopathic Parkinson disease

• Screened for six Gaucher mutations: N370S, L444P, 84GG, IVS+1, V394L, and R496H

99 Ashkenazi Jewish Israeli patients with idiopathic Parkinson disease

• 99 Ashkenazi Jewish Israeli patients with idiopathic Parkinson disease

• Screened for six Gaucher mutations: N370S, L444P, 84GG, IVS+1, V394L, and R496H

31.3% (31/99) patients with Parkinson disease had one or two mutant Gaucher mutations

• 31.3% (31/99) patients with Parkinson disease had one or two mutant Gaucher mutations

• Patients with Parkinson disease had significantly greater odds of being carriers of Gaucher disease than patients with Alzheimer's disease or controls

• Among patients with Parkinson disease, those who were carriers of Gaucher disease were younger than those who were not carriers

96 Ashkenazi Jewish Israeli patients (of the original cohort of 150 DNA samples from Parkinson patients)

• 96 Ashkenazi Jewish Israeli patients (of the original cohort of 150 DNA samples from Parkinson patients)

• 15 carriers: 12 N370S; 2 84GG; 1 R496H

• 1 patient identified: N370S/V394L

• Compared to Parkinson patients with no Gaucher mutation, those with a Gaucher mutation:

• presented earlier with Parkinson disease

• were more likely to have Parkinson-affected relatives

• were more likely to have atypical clinical manifestations

Methods: All patients arriving at the Gaucher Clinic in Jerusalem during the period of mid-October 2011-mid June 2012 (8 months) were interviewed with regard to Parkinson disease in their families.

• Methods: All patients arriving at the Gaucher Clinic in Jerusalem during the period of mid-October 2011-mid June 2012 (8 months) were interviewed with regard to Parkinson disease in their families.

153 GD patients (with 306 obligate carrier relatives) were interviewed

• 153 GD patients (with 306 obligate carrier relatives) were interviewed

• 5.2% obligate carriers (16 / 306) with Parkinson disease

• Another 14 patients had non-obligate carrier relatives (grandparents, uncles, aunts) with Parkinson disease

Mean age onset Parkinson disease among obligate carrier relatives was 66.4 years (range: 45-81 years)

• Mean age onset Parkinson disease among obligate carrier relatives was 66.4 years (range: 45-81 years)

• There was equal incidence of males (50%)

• Among obligate carrier relatives with Parkinson at least 60% obligate carrier relatives with Parkinson disease had the N370S mutation.

8 PD+GD (with 16 obligate carriers) interviewed

• 8 PD+GD (with 16 obligate carriers) interviewed

• 6.3% (1/16) obligate carriers of PD+GD had Parkinson disease

• 5 males (62.5%)

• 5 N370S/N370S (62.5%); 3 N370S/other

• Mean age onset Parkinson disease : 58.9 years (range: 43-75 years)

12 GD+PD patients

• 12 GD+PD patients

• 2.4% (12 / 510) adults at SZMC = GD+PD

• Mean age onset of Parkinson disease = 58.9 years (range: 43-75 years)

• 75% (9/12) are male

• 50% (6/12) of GD+PD are N370S / N370S

Mean age onset Parkinson is later in obligate carriers (66.4 versus 58.6 years)

• Mean age onset Parkinson is later in obligate carriers (66.4 versus 58.6 years)

• No male predominance in obligate carriers (50% versus 75%)

This is the first report of the incidence of Parkinson among obligate carriers of Gaucher disease that implicates:

• This is the first report of the incidence of Parkinson among obligate carriers of Gaucher disease that implicates:

• Later age of onset Parkinson among carriers than patients

• High prevalence of the N370S mutation

• Equal incidence of males and females with Parkinson among obligate carriers