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The Life-and-Death Task of Screening for Jewish Genetic Diseases
It was going to be no big deal — Dr. Scott Zalut was sure of that. But his wife, Jenna, insisted that getting screened for Jewish genetic diseases was important. Zalut felt less compelled. Yes, he knew that one in four Ashkenazi Jews is a carrier for one of the 19 JGDs. During medical school, he had encountered information about many of those diseases. But Zalut was finishing his residency in anesthesiology and working long hours, and the odds of both him and his wife being carriers for the same disease were slim. They decided on what seemed like a logical approach: Jenna would get screened, and if she tested positive for one of the 19, Zalut would then get tested.
Fanconi anemia. That’s the disease for which Jenna tested positive as a carrier. And then, through Einstein Medical Center’s Victor Center for the Prevention of Jewish Genetic Diseases, Zalut also tested positive for it. “Stunned” is the word both of them use to describe their reactions. “And while all of the Jewish genetic diseases are bad, Fanconi anemia is particularly nasty,” Zalut says.
The Victor Center describes Fanconi anemia as a rare blood disorder that causes malformed or missing thumbs, intellectual disability, abnormal skin pigmentation and defective kidneys. By age 7 or 8, bone marrow failure is expected, as is childhood leukemia. Lifespan is limited. Because both of them are carriers for Fanconi anemia, their children have a 25 percent chance of having the disease. “We wanted to have children,” Jenna says, “but we didn’t want them to have a lifetime of illness and pain.”
So the Zaluts faced decisions about having children. Dr. Adele Schneider, director of clinical genetics and medical director of the Victor Center at Einstein Medical Center, emphasizes that undergoing genetic testing gave the Zaluts the ability to make proactive decisions instead of letting biology determine the fate of their family. “Knowledge may be difficult, but it is power,” she says. “That’s what we want to give to every Jewish family. That’s the goal of Screen For Nineteen.”
REACHING OUT TO RABBIS
Screen For Nineteen is an awareness program launched through Victor Centers in Boston, Miami, Atlanta and Philadelphia’s Einstein Medical Center. The goal is to get Jews to undergo screening before they have children so that they can make informed decisions about their family planning. To reach young Jews, the campaign is going where they go: college campuses, at which free screenings have been held, and synagogues, specifically rabbis who officiate at weddings.
In 2013, Screen For Nineteen sent informational packets to 1,600 rabbis in the United States. Included were brochures on the 19 JGDs, posters and pseudo-prescription pads imprinted with information on the nearest genetic testing facilities.
Screen For Nineteen is funded by Pfizer and Protalix BioTherapeutics, an Israel-based company. They enlisted Schneider to provide the information given to rabbis to give to their congregants. Pfizer and Protalix produce pharmaceuticals that treat two JGDs, but the educational materials include information on screening for all 19 diseases.
Why is this program needed? While knowledge of JGDs is not new, it has been for the most part limited to Tay-Sachs. “People are not getting screened as much as we would like because there is a lack of knowledge about what is possible, even within the medical community,” Schneider says. “If an OB-GYN doesn’t have a big population of Jewish patients, the doctor may do what his or her professional association recommends, which is screen for only four genetic diseases.”
Who should be tested? People who have even one Jewish grandparent. “Jewish genes don’t get lost,” Schneider says, “and it is better to have the information and make decisions, than have a child who suffers with a lifetime of illness.”
Having both parents tested is ideal, but one will suffice if finances are an issue, physicians agree. Screening is done via a simple blood test at the Victor Center, Schneider explains. Results are returned within four weeks. The test has a 90 to 98 percent accuracy rate.
Aren’t 19 JGDs a lot? “It does seem so,” Schneider acknowledges. “Nineteen is more than most other population groups carry. Or perhaps it’s that we have discovered more within the Jewish population because they are easier to find among people who intermarry. The good news is that we know what to screen for, and that allows us to take action.”
The 19 JGDs are: Bloom’s syndrome, canavan disease, cystic fibrosis, familial dysautonomia, familial hyperinsulinism, Fanconi anemia type c, Gaucher disease type 1, glycogen storage disorder type 1 A, Joubert syndrome type 2, lipoamide dehydrogenase deficiency (E3), maple syrup urine disease, mucolipidosis type 4, nemaline myopathy, Niemann-Pick disease type A, spinal muscular atrophy, Tay-Sachs disease, Usher syndrome type 1, Usher syndrome type 3, and Walker-Warburg syndrome. (See sidebar for more information.)
Children born with these diseases often end up at Children’s Hospital of Philadelphia under the care of Dr. Marc Yudkoff, chief of CHOP’s division of child development, rehabilitation medicine and metabolic disease. Yudkoff has treated children with JGDs at CHOP for more than 35 years. But neither time nor technology has produced success in treating JGDs. There are therapies for some, cures for none. The majority of JGDs are fatal if no medical care is provided, Yudkoff says.
That care is sometimes delayed because of pediatricians’ misdiagnoses. It’s not through negligence, Yudkoff emphasizes, but through inexperience. Many pediatricians have never seen patients with JGDs, so they don’t think to screen for them. Pennsylvania law mandates that newborns be screened for 29 genetic diseases, but only two of them are JGDs. “That is why it is so important that adults be screened before they have children, so if there is a problem, parents have information to share with their physician,” Yudkoff says.
Even with a proper diagnosis and available treatment, most JGDs affect brain development and create a lifetime of debilitating physical problems. In too many cases, that lifetime is tragically short. “Even with treatment, some Jewish genetic diseases will cause children to die in their infancy,” Yudkoff says.
The most common JGD is Gaucher disease type 1. One in 15 Ashkenazi Jews is a carrier for it, making it more prevalent than Tay-Sachs and cystic fibrosis, the next two most common. According to Einstein Medical Center, Gaucher can cause severe and debilitating symptoms, including enlargement of the liver and spleen, various forms of bone disease, easy bruising, anemia and neurological symptoms.
Yudkoff explains how Gaucher advances through the body. “All healthy genes produce enzymes that cause biological reactions,” he says. “A gene defected through Gaucher can’t produce a specific enzyme, and that causes the body to accumulate fat in the bones, liver and spleen.”
There is a quasi-effective treatment for Gaucher, through a drug produced by Pfizer, but it involves a lifetime of bimonthly infusions. “The medication replaces that missing enzyme,” Yudkoff explains. “It is possible to cleanse the liver and spleen of the accumulated fat. Unfortunately, eliminating the fat from bone has been disappointing and less than effective. But there are new, experimental treatments that look promising.”
Even though the lack of advances in treating JGDs is discouraging, Yudkoff echoes Schneider in touting the effectiveness of screening for them. Not only is knowledge power, he says, but prevention is a form of medicine. In fact, Yudkoff thinks that many prospective parents — not just Ashkenazi Jews — should be tested for genetic diseases. For example, people of Irish descent have a high incidence of being carriers for Tay-Sachs — one in 60, Yudkoff says. They, too, should be screened.
So are we looking at a future in which family planning is dictated by genetic testing? “Well, why not?” Schneider asks. “Why wouldn’t you give your child the best future possible? We’re not saying that people who are carriers for genetic diseases cannot have children with one another. We’re saying that we want to give them information to help them make decisions.”
Which is where Scott and Jenna Zalut found themselves in 2010. Newly informed that they were both carriers for Fanconi anemia, the Zaluts were resolute in their desire to have children. Their question wasn’t if, but how.
CHOICES FOR CARRIERS
What happens if a man and a woman test positive for the same JGD? With technological assistance, they can have biological children. The first option is in vitro fertilization and preimplantation genetic testing, Schneider explains. The couple goes through IVF to create embryos. Those embryos are then tested for the JGD that the parents share. Only the embryos that do not have the disease are implanted into the woman.
Those who have qualms about the use of IVF and possible destruction of embryos should know that Jewish law allows for both, Schneider says. “An embryo has no standing in Jewish law until it is implanted in the womb, and genetic testing is done well before that,” she explains.
But that doesn’t take into consideration the emotional effect of embryo destruction, or the cost of IVF and preimplantation genetic testing. Schneider’s response: “The effects of being the parent of a chronically sick child, watching him suffer and, in all likelihood, die far outweigh the emotional and financial effects of IVF.”
The second option is chorionic villus sampling (CVS). Couples conceive a child the old-fashioned way. When the fetus is 11 weeks old, a physician extracts placental tissue in a procedure similar to an amniocentesis. That tissue is sent to a lab to test it for the specific JGD that the parents carry. Results take at least two weeks, often three.
The math is clear: the fetus can be 13 or 14 weeks old by the time parents learn of its health, and they then need to make a decision about how to proceed. The procedure itself has risks. Because the placenta is invaded, even though it is by a small needle or catheter, there is the chance that disturbing the fetus will result in birth defects or outright miscarriage.
Despite all of the risks, CVS is what the Zaluts decided to do. It took their decision out of the world of statistics and gave them information about their specific fetus. Jenna underwent the extraction when she was 11 weeks pregnant. They waited three weeks for the results. They decided not to tell family or friends about their pregnancy until they got the test results.
And? “The results were negative,” Jenna says. “Our baby did not have Fanconi anemia.” That baby is now a healthy 3-year-old. The Zaluts followed the same procedure for their second child, another boy, born in 2013. “We won the Jewish lottery twice,” Zalut says. “We are incredibly grateful.”
What would they have done if the fetus tested positive for Fanconi anemia? “We didn’t have that conversation,” Jenna says. “My focus was to get through the waiting period and not make myself crazy thinking about the steps after that.”
But the Zaluts didn’t have to stretch their minds to imagine raising a child with a JGD. They had seen it in real life. The rabbi who married them has a son with familial dysautonomia.
THE LIFE OF SAM SERNOVITZ
Long before he became a rabbi, Larry Sernovitz was a student at the University of Pittsburgh, where he became an Alpha Epsilon Pi fraternity brother. In 1992, AEPi held a campuswide, free screening for Tay-Sachs and Sernovitz got tested. His results showed that he was not a Tay-Sachs carrier. Sernovitz didn’t think about JGDs again until 2008, when he and his wife, Rebecca, were expecting their first child. Because they are both of Ashkenazi descent, their OB-GYN suggested that they get genetic testing — on themselves, not the fetus. If they tested positive for a JGD, they could then test the fetus. Because they knew that Sernovitz was not a carrier for Tay-Sachs, they decided that his wife would undergo testing. A few weeks later, the OB-GYN told the Sernovitzes that she was negative for all 19 of the JGDs.
So when Samuel Sernovitz was born in September 2008, his parents were sure that his medical problems had nothing to do with a JGD. “He was failing to thrive and people told us not to worry, that it was just how some babies are,” Sernovitz says. “But we knew something was wrong, and we went from doctor to doctor until a specialist told us to look into familial dysautonomia, or FD. We said it couldn’t be that because my wife tested negative for everything. But then we finally called the OB-GYN who did the testing. It turned out that doctor had not read the results personally. When the paperwork was found, it showed that Rebecca was a carrier for FD. Had we known that she was a carrier, I would have been tested, too. And those tests would have shown that I am also a carrier.”
What would they have done? What they did with Daniella, their nearly 2-year-old daughter. The Sernovitzes conceived her naturally and then, like the Zaluts, did chorionic villus sampling of their daughter’s placenta. It showed that, while she is a carrier for FD, she does not have the disease.
But Sam does. Having FD means that Sam’s nervous system malfunctions, and that results in fluctuating blood pressure and body temperature, an insensitivity to pain and a malfunctioning sphincter and esophagus. His life lurches from one dysautonomic crisis to the next, each including uncontrollable vomiting, sweating, an inability to eat enough food to sustain himself and high then low blood pressure, all of which necessitates hospital stays or, at the least, days in bed. Now 5 years old, Sam has missed half of every school year, and because of that and a learning disability, the natural intelligence that his father describes is stunted.
“I want to be clear that we love our son completely and consider it a blessing that we have him in our lives,” Sernovitz says. “But watching him suffer with illness is incredibly difficult.”
And avoidable. Because of the Sernovitzs’ genetic testing debacle, they are fierce advocates for screening done at places like the Victor Center, not just through OB-GYNs. Sernovitz, now the rabbi at Temple Emanuel in Cherry Hill and a member of the Screen For Nineteen advisory board, believes that it is every rabbi’s duty to discuss genetic testing with couples about to be married. “We have to educate our own community and not leave the responsibility to the doctors,” Sernovitz says. “Rabbis are on the front line of this issue and we can create change.”
Sernovitz doesn’t just discuss screening for JGDs; he insists on it. He will not marry a couple unless they first get tested. “Often, people don’t know that there are 19 diseases and how serious they are,” he says. “But ultimately, every couple wants to have healthy children. No one in my congregation has had a problem with taking the test before I marry them.”
But other rabbis aren’t sure that is the best approach.
Rabbi Jill Maderer of Congregation Rodeph Shalom in Center City is also on the Screen For Nineteen advisory board, but her opinion differs from Sernovitz’s. “I strongly hope that Ashkenazi Jewish couples — and maybe everyone — will get tested for genetic diseases before they get pregnant,” she says. “But I do not feel that couples have to get tested before they get married, nor do I require them to do so.”
To which Sernovitz says: Why not? “Some rabbis don’t want to be that assertive because they think that it will chase away the couple,” he states. “I believe that it empowers them by giving them information. And I believe that it is our duty, as rabbis, to ensure the continuity of the Jewish people by helping people have healthy children and, eventually, eliminating JGDs.”
Sernovitz makes another point: Couples turn to rabbis for premarital counseling but not prepregnancy planning, so rabbis have to intercede during wedding preparations. Here, Maderer sees his logic. “The danger is that they will forget or think it is somehow unimportant, and this alleviates that,” she agrees. “Having couples get tested before they get married is definitely something for me to think about, although I don’t think that I would make it a requirement.”
Rabbi Michael Knopf, the assistant rabbi at Har Zion Temple in Penn Valley, does not believe that couples should be required to get genetic testing before they are married. His wife, Adira, agrees. But they have very different opinions on how a JGD would affect their family planning.
Knopf poses the following scenario to his wife: If they were both carriers for a JGD, would she want to adopt, get pregnant then do CVS, or do IVF and preimplantation genetic diagnosis and use only the embryos without the gene for the disease? Knopf chooses CVS. His wife chooses IVF.
This shocks Knopf. “You wouldn’t rather bear the risk — which is only 25 percent — and have a baby the old-fashioned way?” he asks her.
Absolutely not, she states. “If I could prevent my child from having a lifetime of illness, I would,” she states. “I want to give my child the best life possible from the beginning. Only if we couldn’t afford IVF would I do the testing after I was pregnant.”
Knopf asks, “What if the fetus tested positive?”
His wife doesn’t know if she would terminate the pregnancy or not — and there’s more to it than that. “If I knew that my child was going to be born with a genetic disease, I could be prepared medically and psychologically,” she explains. “I would research it, meet with doctors, prepare the rest of my family and do whatever I needed to do to create those support systems. If there is a medication or a therapy that would help my child, I would be ready with it. I would do whatever it takes.”
Knopf says, “Well, we’ve just discovered the difference in my marriage — and probably in a lot of marriages — about this subject.”
Told of the conversation, Schneider expresses delight. “That’s exactly the point of Screen For Nineteen,” she says. “Let’s hope everyone has these conversations.”
Melissa Jacobs is the former senior editor of Inside and the special sections of the Jewish Exponent. This article originally appeared in Inside Magazine, a Jewish Exponent publication.