How Researchers Uncovered the Gaucher Carrier Rate (Sponsored)
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By National Gaucher Foundation November 29, 2016
Today, researchers are working on complex problems related to Gaucher disease like finding drugs to treat neurological forms of the disease and understanding its complicated relationship with Parkinson’s disease. But 37 years ago, scientists were struggling to grasp how many people even had Gaucher disease, let alone how many were asymptomatic carriers capable of passing it to their children.
In 1979, Edwin Kolodny, MD, professor emeritus at New York University (NYU) School of Medicine, made an incredible discovery – that Ashkenazi Jews had a carrier rate of 1 in 12.5 for Gaucher disease. At the time, other scientists believed the rate to be far lower, and it wasn’t until the arrival of DNA testing years later that the controversy would finally be resolved.
Curious Observations Lead to New Research Questions
Dr. Kolodny began researching lysosomal storage disorders (LSDs) in Dr. Roscoe Brady’s lab in 1967, when Dr. Brady had just recently discovered the enzyme defect responsible for Gaucher disease. After learning techniques for measuring deficiencies in lysosomal enzyme activity, Dr. Kolodny established his own lab in 1970 at the Eunice Kennedy Shriver Center in Massachusetts.
Boston hematologists began sending Dr. Kolodny patients whose bone marrow biopsies revealed the presence of fat-laden Gaucher cells. The doctors wanted to know whether these patients also had a deficiency of glucocerebrosidase (GBA) enzyme, which would indicate Gaucher disease.
Dr. Henry Mankin, a world-renowned orthopedist specializing in hip fracture repair in Gaucher patients, also asked Dr. Kolodny to help by interviewing and examining all of his patients. Dr. Kolodny also began conducting enzyme tests on siblings and other relatives.
Dr. Kolodny observed that many asymptomatic siblings also had little to no GBA activity, and therefore also had Gaucher disease. Ultimately, this observation led to Dr. Kolodny’s study beginning in 1975 to find an enzyme test capable of separating Gaucher patients, carriers and unaffected individuals.
The major sticking point was the overlap in enzyme activity between carriers and those unaffected, which makes it difficult to accurately identify carriers via enzyme test. For 4 years, Dr. Kolodny’s team worked doggedly to develop a complex, highly specialized assay capable of identifying carriers.
He used his method to analyze blood samples from 800 young adults, all healthy individuals of Jewish descent. His surprising results showed that 1 in 12.5 Ashkenazi Jews were Gaucher carriers, even as other geneticists insisted that the number was just 1 in 40.
Gaucher Gene Discovery Confirms a Higher Carrier Rate
When Drs. Mia Horowitz, Ernest Beutler and Ed Ginns independently discovered the Gaucher gene sequence in the late 1980s, Dr. Kolodny knew he might finally be able to prove that carriers were more prevalent than geneticists thought.
Between 1988 and 1990, he spent a total of 12 months on sabbatical working with Dr. Horowitz in Israel developing test methods for identifying mutations in the Gaucher gene. They discovered a variety of Gaucher gene mutations, showing that many different mutations were actually responsible for the disease.
A turning point came in the early 1990s when hematologist Dr. Ernest Beutler and his associates published research on Gaucher carrier incidence based on genetic testing of blood samples from many hundreds of Ashkenazi Jews. Their research showed that approximately 1 in 12 were carriers, proving that among all the previously published estimates, Dr. Kolodny’s earlier prediction by enzyme analysis was closest to the DNA findings.[1],[2]
Continuing Work to Help Gaucher Patients
In the years that followed, Dr. Kolodny continued seeing Gaucher patients and publishing research related to LSDs. Alongside other Gaucher experts, he’s also been involved with Project Hope, a humanitarian program giving patients in developing countries access to life-saving medicines.
Based on his research, Dr. Kolodny believes we’re only seeing the tip of the iceberg when it comes to identifying Gaucher carriers. With so much intermarriage over the centuries, many people are not even aware of their own Jewish ancestry. Gaucher disease affects all ethnic backgrounds, making it important for people with a genetic predisposition or family history of Gaucher disease to get genetic testing for carrier status.
As a neurologist, Dr. Kolodny looks forward to the development of new drugs capable of addressing the devastating neurological symptoms of Gaucher disease types 2 and 3. Well past the usual retirement age, Dr. Kolodny is still publishing papers and giving talks on Gaucher disease, and his work continues to improve our understanding of the disease.
Edwin Kolodny, MD
Dr. Kolodny has treated Gaucher patients for over 30 years as a neurologist both in Massachusetts and New York. A graduate of the NYU School of Medicine, he served as the neurology department chair at the school from 1991 to 2010.
Dr. Kolodny’s research interests center on biochemistry and genetics of LSDs and other nervous system disorders. He has published hundreds of research articles and book chapters, and has received many honors and awards for his contributions to the field of LSD research.
More Information on Getting Tested
Carrier screening for Gaucher disease and genetic counseling can help you determine the risk of passing the Gaucher gene to your children. Get tested today with no out of pocket expenses*.
NGF is working with JScreen to provide carrier screening for more than 100 different diseases, including Gaucher disease.
Visit gaucherdisease.org/screening or call 1-800-925-8885.
*Participant’s insurance will be billed, if applicable. Offer available through December 31, 2016 or when grant funds are depleted, whichever is earlier. Must be between ages 18 and 45. See website for more details.
[1] Zimran A. et. al., American Journal of Human Genetics 1991;49:855-859.
[2] Beutler E. et. al., American Journal of Human Genetics 1993;52:85-88.
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