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Ozlem Goker-Alpan, MD; Grisel Lopez, MD; Joseph Vithayathil, BS; Joie Davis, APRN; Mark Hallett, MD; Ellen Sidransky, MD

Arch Neurol. 2008;65(10):1353-1357.

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.

Author Affiliations: Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute (Drs Goker-Alpan and Sidransky, Mr Vithayathil, and Ms Davis), and Medical Neurology Branch, National Institute of Neurological Disorders and Stroke (Drs Lopez and Hallett), National Institutes of Health, Bethesda, Maryland.

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