Positron Emission Tomography (PET) Imaging in People With Gaucher Mutations

2014-08-27 03:45:43 | BioPortfolio


This study will use positron emission tomography (PET) to compare how people with Gaucher disease or Gaucher disease carriers with parkinsonism, and their family members, use dopamine in their brains in comparison with healthy normal volunteers and people who have Parkinson disease. PET assesses organ function by measuring metabolism. In this study, magnetic resonance imaging (MRI) is used in conjunction with PET to help better interpret and understand the information gleaned from PET.

People 21 years of age and older with the following conditions may be eligible for this study:

- Gaucher disease and parkinsonism

- Parkinsonism and a family history of Gaucher disease

- Gaucher disease and a family history of parkinsonism

- Gaucher disease carriers who have parkinsonism or a family history of parkinsonism

- Unaffected people with a family history of Gaucher disease and parkinsonism

- Healthy volunteers

Participants undergo the following tests and procedures:

- Personal and family medical history

- Physical examination

- PET scan: The subject lies on a table that slides into the PET scanner until his or her head is positioned properly in the scanner. A catheter is inserted into a vein. An initial scan is done to obtain images before radionuclides are injected. Radioactive water is then injected through the catheter and the subject is asked questions in order to stimulate blood flow in certain areas of the brain to show what parts of the brain are activated. Fluorodopa is then infused through the catheter over 3 minutes. The PET scan can last up to 2 hours.

- MRI scan: This test uses a magnetic field and radio waves to obtain images of organs. The subject lies still on a bed in the middle of a circular scanner for about 30 minutes.


An association between Gaucher disease and parkinsonism has been demonstrated by the concurrence of parkinsonian manifestations in over 30 patients with Gaucher disease and an increased incidence of glucocerebrosidase mutations in subjects with parkinsonism. Furthermore, there appears to be a significant number of obligate and confirmed Gaucher carriers with parkinsonian manifestations. Thus, glucocerebrosidase mutations may be a risk factor for development of parkinsonism. However in affected and at-risk individuals, the identification and characterization of early parkinsonian manifestations and the rate of progression of symptoms have not been studied objectively. We propose an in-vivo study of regional cerebral dopamine neurochemistry and blood flow in subjects with glucocerebrosidase mutations. Presynaptic dopaminergic function and cerebral blood flow will be assessed using positron emission tomography (PET) with 6-[F-18] Fluoro-L-DOPA (6FD) and 15 O-H2O in a single PET session. The subjects will include patients with Gaucher disease and Gaucher carriers with parkinsonism, and/or with a family history of a first degree relative with parkinsonism. The control group will include family members lacking glucocerebrosidase mutations, age matched healthy controls, and subjects with parkinsonism without glucocerebrosidase mutations. The kinetic rate constant (Ki) for striatal dopaminergic uptake will be calculated. Using bivariate analysis we will compare the Ki in groups of subjects with glucocerebrosidase mutations, with and without parkinsonian manifestations, with aged-matched healthy volunteers, to identify potential abnormalities in striatal and putamenal presynaptic F-dopa uptake. Each subject will be screened with an MRI to rule-out structural abnormalities, and to further delineate areas of interest in the PET scans. Subjects will also undergo transcranial ultrasonography (TCS) to assess echogenicity of the midbrain. This study will help us to identify abnormalities in L-Dopa uptake in subjects with glucocerebrosidase mutations, to better define the associated parkinsonian phenotype, follow the progression of parkinsonian manifestations and identify "at-risk" indiviuals. The baseline data regarding L-Dopa metabolism in subjects with glucocerebrosidase mutations will enable us to estimate the frequency and earliest onset of parkinsonian symptoms in at-risk subjects. The results of both the PET scans and TCS will be kept confidential, and will not be communicated to the individuals or families involved in the study.

Study Design



Glucocerebrosidase Mutations


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:45:43-0400

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