Rare Disease Report

"Spit Happens": National Gaucher Foundation and JScreen Offer Free Testing Through Year's End

NOVEMBER 22, 2016
Ricki Lewis, PhD
Many years ago, I was thrilled to be part of a panel discussion about genetic testing with Dr. Joseph Ekstein, the Holocaust survivor who founded the confidential genetic testing program Dor Yeshorim in 1983. Their tale is legendary.
After Dr. Ekstein and his wife had their third child with Tay-Sachs disease, he started knocking on doors in his Brooklyn community to urge people out of their complacency and to take action to prevent further cases – the Ekstein’s children weren’t the only ones with the devastating neurological condition. That would be possible, theoretically, by identifying couples in whom both partners were carriers of the same autosomal recessive disease. Still based in Brooklyn, Dor Yeshorim (meaning “upright generation”) has achieved international renown and has banished Tay-Sachs disease from the Jewish community.
The number of identified “Jewish genetic diseases” grew in parallel to research in human genetics. Individual tests for conditions like Canavan disease and familial dysautonomia grew into panels of tests: 8, 12, 22, mostly testing blood cells. Today, JScreen (affiliated with Emory University) tests for 105 recessive conditions, 43 of which occur with greater frequency among people of Jewish ancestry. “Spit Happens” is a riveting short video of Jewish people spitting into tubes to collect a different set of cells, in saliva.
Of course DNA is just a chemical; it doesn’t “know” a person’s religion or ethnic group, and mutations can arise in anyone, not just preferentially in those who attend synagogue. But certain inherited diseases are much more prevalent among certain population groups when the people reproduce only among themselves. Genetic disease risks skyrocket when parents-to-be carry the same mutation from a shared ancestor. The waves of anti-semitism throughout history have repeatedly slashed Jewish populations, each time tightening genetic bottlenecks that concentrated mutations, so that today, any two people of Jewish ancestry are likely fourth or fifth cousins.
Gaucher (“go-shay”) is a classic Jewish genetic disease. It affects 1 in 40,000 in the general population, yet 1 in 450 Ashkenazi (eastern European) Jewish people. One in 10 Ashkenazim is a carrier.
The condition is an enzyme deficiency. Because enzymes enable specific chemical reactions to proceed fast enough to sustain life, when they are deficient, the starting materials build up as the products diminish, much like how the flow of water in a garden hose changes when a knot is tied in the middle. Gaucher disease is also a lysosomal storage disease. The missing enzyme, glucocerebrosidase, normally works in the lysosomes, which are the garbage disposal units inside cells.
One of the materials that builds up in Gaucher disease, ceramide, is deposited in various organs, causing the symptoms of enlarged liver and spleen, bone pain, anemia, and bruising. More than 400 mutations are known, but the condition is classified into just 3 groups based on severity and whether or not the brain is involved. Most cases are type 1, sparing the brain.
Two types of treatments are based on the “garden hose” aspect of the genetic glitch. Enzyme replacement therapy (ERT) does what it says – gives the patient the missing enzyme, in a twice-monthly, very costly, infusion. The first person to be treated with ERT for Gaucher disease in a clinical trial, in 1983, was Brian Berman, who was then 3 years old and had an almost impossibly swollen abdomen. His parents and uncle formed the National Gaucher Foundation, and now Berman, who has 4 children, is the president and CEO in the United States.
A second type of treatment for Gaucher disease is substrate reduction therapy (SRT), which counters the buildup of the starting material, glucocerebroside. The  two SRT drugs, miglustat and eliglustat tartrate, are also the only oral therapies available for Gaucher disease.
The ability to treat Gaucher disease, and the chance of misdiagnosis based on evaluating symptoms alone – bruising can look like leukemia, for example – plus the availability of genetic testing inspired the “Spit Happens” campaign, which will cover all costs not met by insurance for genetic testing. To participate, complete this form by the end of the year.
As Rabbi Ekstein learned, it takes a desire and concerted effort to prevent mutations in the same gene from ending up in the same fertilized ovum. A couple who knows that they each carry such a mutation then has options: adopting; using an assisted reproductive technology such as a sperm or egg donor; or having prenatal diagnosis and then either being reassured that the fetus does not have the condition, or learning that it does and then ending the pregnancy or preparing for the birth of a child who may (or may not: Gaucher’s is variable) have serious symptoms.
Thank you National Gaucher Foundation and JScreen for this opportunity!

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