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Arch Neurol. 2008 Oct;65(10):1353-7. doi: 10.1001/archneur.65.10.1353.

The spectrum of parkinsonian manifestations associated with glucocerebrosidase mutations.

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1
Section on Molecular Neurogenetics, National Human Genome Research Institute, National Institutes of Health, 35 Convent Dr, MSC 3708, Bldg 35, Room 1A213, Bethesda, MD 20892-3708, USA.

Abstract

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.

PMID:
18852351
PMCID:
PMC2629407
DOI:
10.1001/archneur.65.10.1353
[Indexed for MEDLINE]
Free PMC Article
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