Persian Tay-Sachs


In the story, a young prince in an old and distant kingdom is mesmerized with salt.

The prince loves the taste of salt on his tongue, the dryness of it on his skin. He loves the way the grains catch the light as they slip through his fingers like so many tiny pieces of glass on a sun-bleached day. While all the other children in the kingdom are doing what children do, the young prince indulges his fascination with salt. He’s so busy with his adoration, he forgets to grow and yet, even in adulthood, he cannot stop the craving for salt.

Disconsolate over his son’s plight, the king falls ill. In his white palace with emerald windows, his grand wizard, when called upon, ordains that to heal, the king must fall sleep and dream of beauty and youth and conquest. The king dreams he’s young again; he stands in a field of wild grass, watching a beautiful maiden with golden locks run toward him from the edge of the horizon. She’s a fast runner with a graceful step, so light on her feet, he wonders if they ever touch the ground, but the closer she comes to the king, the more slowly she runs. He watches as her gait becomes uneven and her legs fold and she falls to the ground. When it’s time for him to wake up, the king cannot bring himself to abandon the injured and struggling maiden in the grass. The grand wizard calls him; the queen and the prince beckon him; the king will not wake. 

Years ago, in “Cry of the Peacock,” I wrote the story of my own family and of other Iranian Jews I had known or been told about. Most of what I wrote was real, but when the book was published the reviewers evoked terms like “fairy tale” and “magical realism.” I didn’t know what magical realism was, didn’t think I had written a fairy tale. If anyone asked, I tried to explain that what seemed “magical” to the Western ear was just a whole lot of “realism” in the East.

In the land of the slumbering monarch, the queen summons her husband’s army and enjoins them to search the land for a spell that will rouse him from sleep. The bravest of all these men, two brothers, go farther and look more assiduously than all the rest. Everywhere they stop, they tell the story of the boy who won’t grow and the king who won’t wake, and they even tell about the maiden in the king’s dream, how she could outrun the goddess Atlanta until she was betrayed by her own limbs, but no one can help. At the last hour of the last day of their quest, the two brothers encounter two wise men who have come to the kingdom from distant shores, and who claim to have the spell.

I wrote a second book about real events in real people’s lives, and I even wrote a third — this one about all the “magical” things that happen in the far and forgotten corners of these United States — and still, I couldn’t convince most people of the veracity of so much of what happens in the books. Nor did I have a logical explanation for the disconnect. All I knew was that, left alone and forgotten for 3,000 years before they immigrated to the West, Iranian Jews had seen the world become, like Alice’s Wonderland, “weirder and weirder.”

At the palace with the emerald windows, the two wise men draw the king from his sleep and free the prince of the curse of the sorcerer’s salt. And though they cannot save the girl with the faltering gait, they vow to deliver the kingdom of all its unusual maladies. The two wise men have rid other kingdoms of other strange and devastating curses, and they know they can do it again. All they ask for in exchange is a drop of saliva and a tin coin from each of the king’s subjects.

In the late 1990s, two young Iranian Jewish physicians announced the existence of an illness that may be unique to Iranian Jews. At first, hardly anyone believed them. Later, most people thought that even if such an illness did exist, it was so rare as to be irrelevant to the general population. In 2001, Hadassah University Hospital in Israel announced the discovery of a gene that, in its mutated form, can cause a progressive muscular disease that attacks the individual in his 20s; it begins with a weakening of the leg muscles and gradually spreads through the body. The illness is called hereditary inclusion body myopathy, or HIBM. One in 20 Iranian Jews is a carrier of the gene.

Other recessive genetic disorders in Iranian Jews were soon identified: a sensitivity to some forms of anesthesia that can result in death (one in 10 is a carrier); a salt-losing disorder that causes great craving for salt and, if untreated, short stature (one in 30 is a carrier); a hormone deficiency that can lead to, among other ailments, diabetes mellitus type 1 (one in 50 is a carrier).

Although gene mutations exist in every ethnic and racial group, they are more common, and therefore easier to find, in isolated societies with a history of intermarriage. Among Ashkenazi Jews, Tay-Sachs disease was the evil giant that remained latent in a person’s body until he or she produced a child with a partner who was also a carrier of the gene. Tay-Sachs was eliminated in the Ashkenazi population thanks to genetic testing and premarital counseling that were a result of the efforts of two of the world’s leading geneticists, Dr. David Rimoin and Dr. Michael Kaback.

The two wise men stand at the gates of the white palace ready to save the denizens of the old and distant realm. They wait, but no one comes. Bewildered, they send couriers and emissaries into the heartland and repeat their pledge. They sound the bells and call from the highest towers and still, no one answers.

Forty years after spearheading the Tay-Sachs project, Drs. Rimoin and Kaback undertook the task of eradicating Iranian Jewish genetic illnesses. At the Cedars-Sinai Medical Genetics Institute, under Dr. Rimoin’s leadership, Iranian Jewish couples who are planning a family can be tested to make sure they’re not both carriers of the gene; if they are, they can guard against having children who are affected by one illness or another by undergoing in-vitro fertilization and choosing not to implant the defective embryos. Parents with small children can detect some illnesses in time to treat them. And even older people can alert their physicians of their sensitivity to some anesthesia medicines. Testing is entirely confidential, and by law, insurance companies cannot deny coverage or raise rates based on test results. The test costs $350 and requires only a few drops of saliva.

And yet, in the two years since a thousand Iranian Jews were tested under the pilot program at Cedars-Sinai, the phones at the center have remained quiet and few requests have been made for testing. Many Iranian Jews have yet to learn about the diseases or the fact that the genes have been identified. Many fear that by speaking openly about the illnesses and the testing, the community would expose itself to adverse reactions from Ashkenazi Jews. Many do not have the $350 to spare. So far, the dozens of religious and cultural organizations, the nonprofits and all the individual donors who have raised so much for, or given so generously to, one Israeli cause or another, have not been called upon to publicize the testing or finance it for families in need of help. Like the two wise men in the fairy tale that could just as easily be true, Dr. Rimoin and his colleagues at Cedars-Sinai are standing at the gates of our ancient kingdom, ready to break the spell and free us of the sorcerer’s curse.

A hundred years from now, if someone were to write the story of Iranian Jews in Diaspora, the existence of such gene mutations would no longer seem fictional. Nor would the ability of science to eradicate them as it did Tay-Sachs among Ashkenazi Jews. What would seem unreal is if we fail to seize this chance to save ourselves and our children from a fate that, for all its mythical veneer, is bitterly and irreparably real.

For more information on the Persian Jewish Genetic Screening Program, call (310) 423-4461, or visit www.csmc.edu/medgenetics.

Gina Nahai is professor of creative writing at USC. She can be reached at ginabnahai.com.

Dramatic progress in in-vitro detection spurs new push for Ashkenazi Jews to do genetic disease test


Susan and Brad Stillman grew concerned following their son Benjamin’s birth in September 1998. He was fussy and congested, had difficulty breastfeeding and didn’t take to the bottle.

The parents brought him to the pediatrician and then to a hospital pediatric care unit near their home in Rockville, Md., a suburb of Washington.

Benjamin soon was diagnosed with Riley-Day syndrome, now called familial dysautonomia, a genetic disease of the autonomic nervous system that disproportionately strikes Ashkenazi Jews.

When the Stillmans got married in 1995, they were tested for Tay-Sachs disease, the only genetic disease prevalent among Ashkenazim for which screening was available, and neither parent was found to be a carrier or to have the disease.

“Ignorance was bliss,” Susan Stillman said. “We had no idea we were carriers for FD.”

Today, tests are available for 19 chronic conditions that are known as Jewish genetic diseases, including familial dysautonomia. Testing capabilities have risen dramatically: Just one year ago, individuals could be tested for 16 conditions; in 2009, the number was 11. Among those conditions, in addition to FD and Tay-Sachs, are cystic fibrosis, Gaucher disease, Canavan disease and Niemann-Pick disease.

Organizations dealing with Jewish genetic diseases are intensifying their efforts to educate Ashkenazim of childbearing age about the need to be screened for all 19 conditions with a single blood test, and to update tests that have already been conducted. The experts view this as a serious communal health issue, with one in five Ashkenazim estimated to be a carrier of at least one of the 11 diseases that could be tested for in 2009.

A study by New York University’s Mount Sinai School of Medicine in Manhattan found that significant numbers of New York-area Ashkenazim —one in every 3.3 — are carriers of at least one of the 16 diseases tested for last year.

A carrier rate of one in 100 for an individual disease would be “of concern,” said Dr. Adele Schneider, director of clinical genetics at Philadelphia’s Victor Centers for Jewish Genetic Diseases.

As with any genetic disease, when both parents are carriers, each of their children will have a 25-percent likelihood of being affected; the more diseases for which each parent is a carrier, the greater the odds of the children being affected.

“If you and your spouse find out that you’re carriers, you may not want to take that one- in-four chance,” said Karen Litwack, director of the Chicago Center for Jewish Genetic Disorders. “It’s a terrible ordeal for parents to go through. From a Jewish community standpoint, there’s a general consensus that education and outreach will, hopefully, prevent this kind of thing from happening.”

Experts in Jewish genetic diseases are seeking to promote awareness of the potential problems, because screening before a pregnancy can offer options for preventing or dramatically reducing the chance of a child being born with a disease. The four main alternative options are utilizing a sperm donor; utilizing an egg donor; pre-implantation genetic diagnosis (in-vitro fertilization of the mother’s egg, analysis of the embryo, and implantation only if the embryo is healthy); and even aborting a fetus affected by both parents’ disease-carrying genes.

“Screening is protecting future generations,” said Randy Yudenfriend-Glaser, who chairs the New York-based Jewish Genetic Disease Consortium. She is the mother of two adult children with mucolipidosis type IV, one of the known Jewish genetic diseases.

“When you’re young and getting married, you don’t want to know about it because it’s scary,” she said. “But you should want to know about it.”

Experts also emphasize the need for each carrier to be screened prior to each pregnancy to account for additions to the screening panel in the interim.

Several organizations are expanding their outreach to rabbis and Jewish communal leaders to enlist their help in persuading prospective parents to get tested. Even doctors don’t push sufficiently for testing, representatives of these groups say.

The Victor Centers’ survey in April of 100 Atlanta-area obstetricians, gynecologists, primary care physicians and pediatricians found that only 51 percent routinely recommend preconception screening, and just 34 percent recommend updated screenings between pregnancies. Not a single respondent reported recommending screening for more than six of the 19 known diseases.

The findings were “stark” and “very worrisome,” said the Victor Centers’ national project director, Debby Hirshman.

The agency’s Atlanta Jewish Gene Screen program has secured the agreement of area rabbis to distribute fact sheets to the 17,000 congregants expected to attend High Holiday services next month.

The Jewish Genetic Disease Consortium, with the support of the New York Board of Rabbis, last September inaugurated a clergy awareness program.

Several rabbis have taken the effort to spearhead educational efforts into their own hands. Rabbi Peter Kasdan, a Reform rabbi from New Jersey who has moved to Florida in retirement, has made it a requirement that couples undergo testing before he performs their weddings. Rabbi Larry Sernovitz of Philadelphia’s Old York Road Temple-Beth Am, whose son was born with familial dysautonomia, successfully lobbied the Union for Reform Judaism to host a session on Jewish genetic diseases at its upcoming convention in Washington. Rabbi Joseph Eckstein, who lives in New York, lost four children to Tay-Sachs disease, and in the 1980s he founded Dor Yeshorim, a Brooklyn-based organization that promotes screening in Orthodox communities.

In August, the Victor Centers rolled out an iPhone and iPad application it has developed with information on Jewish genetic diseases.

The outreach efforts mean a lot to Stillman. Last week, she spoke about her situation during a panel discussion at the 31st IAJGS International Conference on Jewish Genealogy in Washington. Stillman described her son as a sweet, loving child. Benjamin, who is entering the eighth grade, plays piano and plans to celebrate his bar mitzvah in September. But he’ll always have to eat through a feeding tube and to receive daily medication.

Stillman isn’t sure if Benjamin can live independently, marry or have children.

“I don’t know how long my child will live. I can’t look too far down the road—only half the kids live to age 30,” she said of those diagnosed with familial dysautonomia. Her presentation at the genealogy conference, Stillman said, had one goal: raising awareness.

“It can happen to you,” she said. “I am a regular person. It happened to me.”

A Decrease in Vigilance


A conference on genetic diseases held by the Cultural Foundation of Habib Levy in November led The Journal to examine the Jewish community’s reduced state of awareness about genetic testing for prospective parents. During the past 30 years, large-scale genetic screening of Ashkenazi Jews in the U.S., Israel and other countries has reduced the number of babies born with Tay-Sachs, the most widely known Jewish genetic disease, by 90 percent. Yet today, younger Jews are less conscious of Tay-Sachs and even less aware of testing made available during the past five years for a newer array of genetic diseases. Geneticists and physicians confirmed that many people are not adequately informed about their genetic testing options. Regardless of their educational background, few individuals know if they fall into a high-risk category for genetically transmitted diseases. Experts interviewed maintain there has been a relaxation in vigilance about carrier screening and a consequential rise in danger signals for American Jews of Ashkenazi descent.

Dr. Dana Eisenman, a general internist with the Health Source Medical Group who spoke at the November conference, outlined some of the major genetic diseases that Jews need to be tested for: Tay-Sachs, Niemann-Pick, Gaucher, Canavan and cystic fibrosis. “Gaucher is the most common genetic disease in Jews,” he said, “but it is less well-known than Tay-Sachs. Unlike Tay-Sachs, symptoms such as anemia, bone pain and fractures don’t often show up until adulthood. For this disease there is replacement enzyme available that reverses many of these symptoms.”

Cystic fibrosis causes mucus to build up in the bronchial tubes and the digestive system to fail to absorb nutrients. “In Ashkenazi Jews,” Eiseman explained, “the carrier rate is one-in-40. As with the other genetic diseases, there is a 25 percent chance of a baby having the disease. Malnutrition and lung failure usually lead to death by the age of 30.”

Tay-Sachs and Niemann-Pick, both caused by enzyme deficiencies, result in progressive brain damage and mental retardation from infancy, with death usually occurring in early childhood. Some variants of Niemann-Pick, which causes enlargement of the liver and spleen, turn up in older children, and one type does not affect the brain.

Unless there is a family history of one of these diseases, the issue of carrier genetic testing usually arises with a decision to have children. Until recently, the only commonly available tests were Tay-Sachs for Jews and sickle cell trait screening for African Americans. Eisenman stressed that today carrier genetic testing is available for all of these diseases.

“Each cell in our body has two sets of genes,” he explained, “one set inherited from our mother, one set from our father. In most cases, only one normal gene of a pair is necessary for a cell to function normally. And so if a person has one defective Tay-Sachs gene from his mother but a normal gene from his father — one bad gene, one good gene — he will not have the disease. Now if the woman is also a carrier, each of the children of this couple has a one in four chance of having the disease.

“Through carrier genetic testing, the prospective parents can identify high risk pregnancies and then decide what to do,” Eisenman said. “Any couple should avail themselves of all the tests for these rare diseases that could affect the fetus. Most insurance plans will cover these, if you’re persistent about it.”

Later, in a follow-up interview, Eisenman said that “it’s really the diseases other than Tay-Sachs that are being ignored. I believe they should all be tested, even though the risk is maybe one in a thousand. If the mother is tested and she’s negative, then it really doesn’t matter what the father is.

“Probably the biggest threat to health resources is cystic fibrosis,” he added. “One couple came from a family of doctors, but weren’t aware of it and didn’t test for it. One in every thirty white people carry the gene of cystic fibrosis. So that is probably the most important one to be tested.”

“There’s a decreased vigilance in the Jewish community even regarding Tay-Sachs,” said Dr. Judith Tsipis, professor of biology and director of the genetic counseling program at Brandeis University. “I think that one in 25 Ashkenazi Jewish individuals are carriers of Tay-Sachs. In the late l960s, they developed a biochemical test to find out if someone was a carrier or not, and that enabled couples to make informed reproductive decisions. At that time a lot of people knew families who had children with the disease; it was very much on people’s minds.

“What has happened is that the program has been spectacularly successful,” Tsipis continued. “But the next generation no longer has that sensitivity to the issue, and they’re still genetically at risk. College students, young couples getting married, rabbis counseling couples are not mentioning the possibility of carrier testing the way they used to. And that’s a pretty disturbing trend. I certainly know of several couples who were not informed and who had children with Tay-Sachs recently.”

Screening for Canavan disease — also known as spongy degeneration of the brain — is now urgently recommended, Tsipis stressed. “Whenever Tay-Sachs is discussed, Canavan should be discussed,” she said. Canavan strikes one in 6,400 children, and there are only about 200 children in the U.S. with the disease. But once a child inherits two copies of the Canavan gene, the child’s brain inexorably deteriorates, wiping out thinking, feeling, emotions, vision and muscle control. As the disease progresses, it causes seizures, severe feeding problems, retardation and blindness. Most children die between ages 10 and 15.

Tsipis — whose son died of Canavan disease in 1998 — explained the real story is the overall lowered awareness in the Jewish community: “You don’t need to have a family history in order to be a carrier and at risk. People say, ‘Gee, I don’t need to be tested. I have no relatives with Tay-Sachs.’ But that’s not the way recessive inheritance works. It’s two families coming together.”

Dr. Ellen Knell, a geneticist at the conference who specializes in cancer risk assessment, underscored the concerns of Tsipis. “An awful lot of the young people who are of child-bearing age do not even know about Tay-Sachs,” Knell told The Journal. “When the screening program was new, everybody got screened and everyone knew about it. But when have you last heard about it? ”

Knell also pointed to the need to test for all of the five major diseases.

“The bottom line is that these diseases still happen,” she said. “The carrier rate for Tay-Sachs is the same as it has always been, and there are about eight things one can do to not have a Tay-Sachs baby. The same applies to the other diseases as well. Depending on how religious you are, you can choose prenatal detection, with the option of aborting an affected child, because three-fourths will be normal. You can choose to have a donor sperm, artificial insemination from an unknown nonspouse. If you are very religious and are against these procedures, you can be anonymously tested and be introduced to someone who is not carrying the same mutations you might have. So there’s a range of options. The important thing to me is that if you’re unaware of all this and don’t have any testing at all, you may have an unpleasant outcome that you were not aware could occur.

“Look,” Dr. Knell said. “The only two ways that you find out if you’re a carrier of an abnormal gene is one, to be tested or two, to have a child with that disease. Most people would choose not to bear and give birth to a baby that’s going to die in three to five years. This is not past history. This is something that still needs to be dealt with. People are still getting these diseases.”

For information about support groups related to genetic diseases:

National Tay-Sachs & Allied Diseases
Association, Inc.

2001 Beacon St.,
Suite 204
Brighton, MA 02135
(800) 906-8723
(617) 277-4463
http://www.ntsad.org

National Society of Genetic
Counselors

233 Canterbury Drive
Wallingford,
PA 19086
(610) 872-7608
www.nsgc.org

National Foundation for Jewish Genetic
Diseases

250 Park Ave.
New York,
NY 100ll
www.nfjgd.org

National Niemann-Pick Disease
Foundation

3734 East Olive Ave.
Gilbert, AZ 85234
(920) 563-8677
(877) 287-3672
www.nnpdf.org