J Clin Neurol.  2011 Jun;7(2):99-101. 10.3988/jcn.2011.7.2.99.

Parkinsonism Associated with Glucocerebrosidase Mutation

• Sunwoo MK
• Kim SM
• Lee S
• Lee PH

• KMID: 2178974
• DOI: http://doi.org/10.3988/jcn.2011.7.2.99

Abstract

BACKGROUND
Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the beta-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations.
CASE REPORT
A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. 18F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen.
CONCLUSIONS
This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation.

Keyword

Gaucher's disease; glucocerebroside; Parkinson's diseases

MeSH Terms

Adult
Arm
Carcinoma, Ductal
Dopamine Agents
Dopamine Plasma Membrane Transport Proteins
Female
Gait Disorders, Neurologic
Gaucher Disease
Glucosylceramidase
Heterozygote
Humans
Hypokinesia
Lysosomal Storage Diseases
Paresthesia
Parkinson Disease
Parkinsonian Disorders
Positron-Emission Tomography
Risk Factors
Siblings
Stress, Psychological
Tremor
Dopamine Agents
Dopamine Plasma Membrane Transport Proteins
Glucosylceramidase

Figure

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  Fig. 1 Immunohistochemical analysis with CD-68 antibodies. Numerous lipid-containing Gaucher cells, which were positive for CD-68 staining, have infiltrated the bone marrow.

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  Fig. 2 Genetic analysis of GBA and dopamine-transporter imaging. Direct polymerase chain reaction sequencing revealed double mutations of S271G (p.Ser310Gly) and R359X (p.Arg398Term) in GBA in patient 1, and the R359X mutation in patient 2 (A). 18F-FP-CIT PET revealed decreased uptake of dopamine transporter in the posterior portion of bilateral putamen, which was more severe on the right side (B). GBA: β-glucocerebrosidase, 18F-FP-CIT: 18F-fluoropropy-lcarbomethoxyiodophenylnortropane, PET: positron-emission tomography.

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