At age 34, Jennifer has a life many women would envy: a loving husband, a beautiful 2-year-old son and a flourishing career. But every morning when she wakes up, the first thing she asks herself is what might have deteriorated in her body overnight. When she walks, she is careful not to fall into anyone near her. And when her son rushes to greet her, she can’t rush back.
Jennifer, who, like others interviewed for this article asked that her real name not be used to protect her privacy, has hereditary inclusion body myopathy (HIBM), a disease that causes muscles to become progressively weaker over time. In the general population, it’s rare. But in the Iranian Jewish community, it’s so prevalent that researchers at Cedars-Sinai Medical Genetics Institute here in Los Angeles were prompted to launch a targeted genetic screening program, conducted last summer, to test for it, along with three other disorders that affect the Iranian Jewish community at a disproportionate rate.
Led by Dr. David Rimoin, director of the Medical Genetics Institute at Cedars-Sinai, researchers hoped to find out whether genetic traits in Iranian Jews in Los Angeles mirror traits found in Israeli Iranian Jews that were reported beginning in the 1970s.
By the 1990s, Israeli geneticists discovered that nearly one in four individuals of Iranian Jewish heritage are carriers of one of the genetic mutations that can cause either an inherited blood plasma enzyme abnormality (pseudocholinesterase deficiency), which can lead to a sensitivity to certain anesthesia; a salt-losing disorder (congenital hypoaldosteronism); a multiple hormone deficiency (polyglandular deficiency); or HIBM.
It’s unclear exactly why these particular diseases have permeated the Iranian Jewish community, but many ethnic groups that have remained somewhat isolated throughout history face similar odds.
“Every ethnic group has the same frequency of genetic diseases,” Rimoin said, but the diseases themselves vary from one ethnic group to another.
To launch the pilot program, Rimoin enlisted the help of Dr. Michael Kaback, a professor at UC San Diego and a medical genetics consultant at Cedars-Sinai. The two teamed up 40 years ago to pioneer genetic screening for Tay-Sachs in the Asheknazi Jewish population, and the protocols they established during that project proved an excellent starting place for their current effort.
Beginning in July of this year, volunteers from the Iranian Jewish community were anonymously screened at synagogues, community centers and at Cedars-Sinai. By early this month, 1,000 people had been tested.
The results, Kaback said, were not surprising.
“These genes are as frequent, if not even more frequent, as what was reported in the Israeli population.”
For the L.A. Iranian Jewish community, the beneficial implications of this study are tremendous. If detected, three of the four diseases can be treated before they cause significant problems, and HIBM, which currently has no treatment or cure, could be significantly reduced over time through pre-natal screenings.
Demonstrating the prevalence of these disorders also means that genetic testing will likely become available in doctors’ offices — as Asheknazi Jewish panels are now — and that insurance companies might eventually cover the testing, which can cost thousands of dollars if paid for out-of-pocket.
All four disorders are recessive, meaning that in order to pass it along to a child, both parents have to be carriers, and that it’s important for couples to know their status if they plan to have children. A child with carrier parents has a 25 percent chance of being affected, a 25 percent chance of not inheriting mutated genes at all and a 50 percent chance of being a carrier but not affected.
If a person discovers that he or she is affected, or if a couple discovers that their child will be affected, they can take appropriate steps to ensure that symptoms are managed.
For instance, pseudocholinesterase deficiency (anesthesia sensitivity), for which one in 10 Iranian Jews are carriers and therefore one in 400 are affected, causes difficulty breaking down certain anesthetic agents and so impairs recovery time after surgery. Symptoms can be avoided altogether by simply using different anesthetic agents. But if it’s undetected, symptoms can be shocking.
“I’ve had women come to me who couldn’t move their legs for three days after an epidural during pregnancies,” Rimoin said.
Sarah, 56, discovered that she was affected by anesthesia sensitivity after participating in the Cedars study.
“I’m very happy that I know,” she said, adding that her brother and cousins are also affected. She also discovered that two of her four children are carriers.
Of the four diseases, HIBM is the most severe and the only one for which neither a treatment nor a cure is available. The onset of HIBM usually occurs in a person’s 30s, but can start as early as their 20s or as late as their 50s. As muscles deteriorate, many patients lose their ability to walk altogether. One in 20 Iranian Jews are carriers of the genetic mutation that causes HIBM, meaning that approximately one in 1,600 will have the disease.
Since it can’t be treated, the only way to address HIBM is through genetic testing and counseling. Couples who are both carriers can undergo prenatal testing or preimplantation testing, in which the woman’s eggs are fertilized and tested outside the uterus, thereby avoiding having to make a difficult decision about an existing pregnancy.
Many in the HIBM community believe that genetic screening is something that the Iranian Jewish community should embrace.
“[It] is invaluable,” said Jennifer, who since finding out about her disease had her son tested. “I think it’s a mitzvah. Know what you’re dealing with, and then you can make an informed decision.”
In the Iranian Jewish community, though, as with many tight-knit communities, genetic screening is not without its difficulties.
“People are scared,” said Gila Michael, chair of the Neuromuscular Disease Foundation, an organization that helps raise funds and awareness about HIBM. “Many don’t want to deal with” the high risk of inheriting these diseases. There’s the fear of being stigmatized, she added, and the fear of taking oneself or one’s children out of the marriage pool within the community.
Still, Rimoin and Kaback are hopeful that their findings, along with community education, will lead to a better understanding of the diseases and of the community’s risk. And based on the results of their work with Tay-Sachs, which, a generation later, has been reduced by over 95 percent among American and Canadian Ashkenazi Jews, they have high expectations for success.
Moving forward, Rimoin hopes to bring the Iranian Jewish testing to college campuses in order to screen individuals and couples as they enter their reproductive years. Eventually, he’d like to develop testing for more ethnic groups, including “the African American community, the Italian community, the Chinese community and others.”
Kaback adds that the most important thing that can come out of this project is for people to take control of their health and become educated. “What we’re trying to do is to get people informed,” he said, “so they can make their own decisions.”
For more information on testing or becoming involved, contact Cedars-Sinai at (310) 423-4461.