The connection between ERAD, UPR, Gaucher disease and Parkinson disease

Mutations in GBA which are causative of Gaucher disease in their biallelic form, are the most common genetic risk factor for Parkinson disease. The diagnosis of Parkinson disease relies upon clinically defined motor features which appear after irreversible neurodegeneration. Prodromal symptoms of Parkinson disease may provide a means to predict latent pathology, years before the onset of motor features. Previous work has reported prodromal features of Parkinson disease in GBA mutation carriers, however this has been insufficiently sensitive to identify those that will develop Parkinson disease. The Remote Assessment of Parkinsonism Supporting Ongoing Development of Interventions in Gaucher Disease (RAPSODI) study assesses a large cohort of GBA mutation carriers, to aid development of procedures for earlier diagnosis of Parkinson disease.

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Type I Gaucher Disease and Parkinsonism: Prevalence of Parkinson Disease among Ashkenazi Family Members Who Are Carriers of Gaucher Disease.

Blood ◽

10.1182/blood.v106.11.3871.3871 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3871-3871

Author(s):

Hanna Rosenbaum ◽

Judith Aharon-Peretz ◽

Ruth Gershoni-Baruch ◽

Jacob M. Rowe4

Keyword(s):

Family History ◽

Parkinson Disease ◽

Gaucher Disease ◽

Medical Center ◽

Family Members ◽

Carrier State ◽

High Rate ◽

Type I ◽

History Of ◽

Gba Mutations

Abstract Background: An association between patients suffering from Parkinson Disease (PD) and type I Gaucher disease (GD) was previously described (N Engl J Med, 2004). The goals of the present study were to report the frequency of Parkinson disease among the clinically unaffected family members of Ashkenazi GD patients who are obligate or known glucocerebrosidase (GBA) mutations carriers, and evaluate the clinical course in Type I GD carriers with concomitant manifestations of Parkinson disease (PD). Methods: A cohort of forty three consecutive unrelated Ashkenazi Type I GD patients followed at the hematology department in the Rambam medical center in Haifa, Israel were evaluated for a family history of PD. Results: Among forty-three families of Ashkenazi GD patients twelve had one or more relatives with PD. All these subjects were known obligate or identified as (GBA) mutation carriers for one of the common mutations among the Ashkenazi Jewish population namely N370S, 1604 or 84GG. The age of PD onset among GD family members carriers of GBA mutation ranged from 40 to 67 years with a mean of 53 years. Conclusions: A high rate of relatives with PD was found among GD patient’s families. These results reinforce the association between GD carrier state and PD and suggest that glucocerebrosidase mutations might predispose to PD. PD in family members of Ashkenazi GD patients Age Genotype PD family history Age onset * GF - Grandfather 18 84GG/1604 mother & 2 GF* 50;55 20 84GG/1226 grandfather 50 59 1226/1226 2 uncles 55 31 1226/1226/no sister 46 18 1226/1226 grandmother 65 27 1226/1226 mother 52 18 1226/1226 father & aunt 70 32 1226/1226 2 aunts (identical twins) 55;67 40 1226/1226/no aunt 65 61 1226/1226 mother 40 8 1226/1226 grandfather 70 13 1226/1226 mother & aunt 60;64

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