The Spectrum of Parkinsonian Manifestations Associated With Glucocerebrosidase M

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The Spectrum of Parkinsonian Manifestations Associated With

Glucocerebrosidase Mutations

October 2008

Background Mutations in the glucocerebrosidase gene (GBA) result in

Gaucher disease and can be associated with a phenotype characterized

by adult-onset progressive neurologic deterioration and parkinsonism.

Objective To define the clinical and neurologic spectrum of

parkinsonian manifestations associated with GBA mutations.

Design, Setting, and Patients A prospective case series of 10

patients (7 men and 3 women) with parkinsonism and GBA mutations

evaluated at the National Institutes of Health Clinical Center.

Main Outcome Measures The GBA genotypes were identified by means of

DNA sequencing. Tests evaluating neurologic, motor, cognitive,

ocular, and olfactory functions were performed and the results were

analyzed by a single team.

Results Genotyping identified GBA mutations N370S, L444P, and

c.84dupG and recombinant alleles. The mean age at onset of

parkinsonian manifestations was 49 years (range, 39-65 years),

disease duration was 7.8 years (range, 1.2-16.0 years), and Unified

Parkinson Disease Rating Scale part III score was 26.3 (range, 13-

38). Half of the patients reported cognitive changes later in the

disease course. Six patients were diagnosed as having Parkinson

disease, 3 as having Lewy body dementia, and 1 as having a " Parkinson

plus " syndrome. The most frequent nonmotor finding was olfactory

dysfunction. Atypical manifestations included myoclonus,

electroencephalographic abnormalities, and seizures.

Conclusions In the homozygous and heterozygous states, GBA mutations

are associated with a spectrum of parkinsonian phenotypes ranging

from Parkinson disease, mostly of the akinetic type, to a less common

phenotype characteristic of Lewy body dementia.

Source:

http://archneur.ama-assn.org/cgi/content/short/65/10/1353