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People with Gaucher Disease at Seven to Nine Percent Risk of Developing Parkinson's

Researchers have shown that people with two faulty copies of the gene involved in Gaucher disease, who are already known to have higher risk of Parkinson’s disease, develop PD at a younger age (about 10 years earlier) than those with only one or no defective copies. The study funded, in part, by the Parkinson’s Disease Foundation (PDF) and published online April 21 in JAMA Neurology, could help scientists better understand the genetic links between the two diseases.

Gaucher disease is the most common genetic disorer among Ashkenazi Jews.  It may present with easy bruising, fatigue, anemia, low blood platelets, enlargement of the liver and spleen or bone pain. It is caused by a deficiency of the enzyme glucocerebrosidase, which is produced from the GBA gene. The disease develops when both copies of the GBA gene are mutated. A mutation in one of the two copies of the gene was long thought to be harmless; however, recent research has shown that people who are carriers of this single genetic mutation have five times the normal risk of developing Parkinson’s disease.

A team of researchers in Israel and the United States, led by Roy Alcalay, M.D., at the PDF Research Center at Columbia University Medical Center, wondered whether having two mutated copies of the GBA gene would increase people’s risk of PD to a greater extent than having only one mutated copy. They also wanted to compare the ages at which people developed PD. Since mutations in the GBA gene are more common among Ashkenazi Jews (one in 15 people is a carrier), researchers studied the overlap between GBA mutations and PD in this community.

Dr. Alcalay and his colleagues recruited 427 Ashkenazi Jews with Gaucher disease from two medical centers, one in Jerusalem and one in New York City. Because the parents of people with Gaucher disease are carriers of the GBA mutation, the researchers also included 694 parents of the people with Gaucher, each of whom had only one mutated copy of GBA. They also studied 154 parents of unrelated people with no GBA mutations or PD as the control group from Columbia University. The researchers examined the occurrence and age of onset of PD in each of the three groups.


  • The risk for PD was higher in the two groups with GBA mutations – both those with one copy (carriers) and those with two copies (living with Gaucher) – than in the control group with no GBA mutations. 
  • People with Gaucher disease did not have a significantly higher risk of PD than GBA carriers.
  • Among those who developed Parkinson’s, those with Gaucher (two mutated copies of GBA) developed the disease 11 years before the carriers (one mutated copy of GBA), an average age of 54 versus 65 years. The control group developed PD at an average age of 72 years.
  • The risk for developing PD at age 60 was 4.7 percent for people with GD, 1.5 percent for GBA carriers, and 0.7 percent for the control group. At age 80, the risk for developing PD was 9.1 percent for people with Gaucher disease, 7.7 percent for GBA carriers, and 2.1 percent for the control group.

What Does It Mean?

Doctors have long noticed an association between Gaucher disease and Parkinson’s disease. It is well established that carriers of a single Gaucher (or GBA) mutation have a risk factor for developing PD.

The current study provides new information on the actual risk for PD both among people with Gaucher disease (two copies of the mutated GBA gene) and people who are carriers (one copy of the mutated gene). While the researchers hypothesized that the risk for PD would be much higher among the first group, people with two copies, unexpectedly both groups had an equivalent risk of developing PD. This risk was higher than the risk for people who lacked any GBA mutations.

Additionally, the number of mutated GBA copies did have an impact on the age of PD onset. People with GD developed PD at an earlier age than GBA carriers, who in turn developed PD at an earlier age than non-carrier controls. This result suggests that carrying a second mutated GBA copy can cause PD to develop at an earlier age than a single mutated copy, rather than increasing the overall PD risk.

This new information may be very helpful for people who know they are Gaucher carriers, for example people who get tested for mutations in this gene as part of prenatal genetic testing (testing for this gene is included in the prenatal genetic testing recommended for those of Jewish ancestry).

Furthermore, a better understanding of the link between Gaucher and PD may shed light on what causes PD in general. Gaucher is a well-studied disease that results from a loss of an enzyme glucocerebrosidase and the missing enzyme is available at a treatment for Gaucher disease. Scientists still do not know how mutations in the GBA gene contribute to PD, but it is possible that under normal conditions, the enzyme produced from the GBA gene, glucocerebrosidase, helps to clear toxic clumps of alpha-synuclein from the brain. If this is the case, when one or both copies of GBA are mutated, the mutations cause the enzyme to malfunction, which in turn causes alpha-synuclein may build up, leading to PD. However, this hypothesis has not yet been proven experimentally.

This study may help doctors and genetic counselors advise people with one or two mutated copies of GBA about their PD risk. However, it is important to note that most people with GD and most GBA carriers (more than 90 percent) will never develop PD.

Reference: Alcalay RN, Dinur T, Quinn T, Sakanaka K, Levy O, Waters C, Fahn S, Dorovski T, Chung WK, Pauciulo M, Nichols W, Rana HQ, Balwani M, Bier L, Elstein D, Zimran A (2014) Comparison of Parkinson Risk in Ashkenazi Jewish Patients With Gaucher Disease and GBA Heterozygotes. JAMA Neurol. DOI: 10.1001/jamaneurol.2014.313

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Source Date: May 16 2014