The spectrum of parkinsonian manifestations associated with glucocerebrosidase mutations.

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.

• Authors: Ozlem Goker-Alpan, Grisel Lopez, Joseph Vithayathil, Joie Davis, Mark Hallett, Ellen Sidransky
• Journal: Archives of neurology (Arch Neurol) Vol. 65 Issue 10 Pg. 1353-7 (Oct 2008) ISSN: 1538-3687 [Electronic] United States
• PMID: 18852351 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Glucosylceramidase

Topics

• Adult
• Age of Onset
• Aged
• Cognition Disorders (diagnosis, genetics, physiopathology)
• DNA Mutational Analysis
• Disability Evaluation
• Female
• Gaucher Disease (complications, enzymology, genetics)
• Gene Frequency
• Genetic Predisposition to Disease (genetics)
• Genetic Testing
• Genotype
• Glucosylceramidase (deficiency, genetics)
• Humans
• Lewy Body Disease (diagnosis, genetics, physiopathology)
• Male
• Middle Aged
• Mutation (genetics)
• Olfaction Disorders (diagnosis, genetics, physiopathology)
• Parkinsonian Disorders (enzymology, genetics, physiopathology)
• Phenotype
• Prospective Studies