Miryam Z. Wahrman, Ph.D.
"Tay-Sachs Alert", declared the ominous advertisement which ran recently in several Jewish newspapers in the New York metropolitan area. The ad further explained, "If someone in your family was tested for the Tay-Sachs gene and the test was screened by Corning Clinical Laboratories, MetPath, MetWest or Quest Diagnostics between 1992 and 1998, please contact us to determine whether you need to schedule a free retest to confirm your results. For women and couples who are pregnant or plan to become pregnant, we urge you to contact us immediately."
Unfortunately, this alert was too late for three unfortunate couples who, despite being tested and informed that they were noncarriers, went on to have Tay-Sachs babies.
"It's a voluntary retesting program," reported Gary Samuels, spokesman for Quest Diagnostics. He explained that of the approximately 36,000 tests administered between 1992 - 1998, "we are aware of three [Tay-Sachs babies who were born]."
Babies with Tay-Sachs appear healthy for the first few months of life, then begin to deteriorate, losing mental and physical abilities. As the disease progresses, the child becomes blind, deaf, unable to swallow, and eventually paralyzed, usually dying by ages 3 to 5.
The most common test to determine carrier status relies on the ability to detect levels of the enzyme hexosaminidase A in the blood. A deficiency in that enzyme leads to a buildup of lipids in the nervous system resulting in irreversible damage to nerve cells. One in twenty-five Ashkenazi Jews is a carrier of the disease and can transmit a single copy of the gene to their offspring. When both parents are carriers, each child has a 25 percent of inheriting two copies of the gene, and thus getting the disease.
The three types of tests which are now available include a blood serum test for the enzyme, a leukocyte (white blood cell) test for the enzyme, and a DNA test. The Mount Sinai Center for Jewish Genetic Diseases advertises that its carrier screening for Tay-Sachs disease which uses enzyme tests has a "detection rate for carriers [of] approximately 99%".
Another commercial company involved in Tay- Sachs testing, Genzyme Genetics, reports a 98% sensitivity of their enzyme test, but only a 94% detection rate using DNA testing. This is because DNA tests are so specific that not all types of mutations are identified within the test. Thus, people with different mutations of that gene would go undetected. For that reason, Genzyme Genetics does not recommend using the DNA test alone, but rather in combination with, or as a confirmation of the enzyme test results.
"I was sad to hear what happened, but I wasn't surprised," commented Shari Ungerleider, referring to the Tay-Sachs retesting program. The Ungerleiders were tested for Tay-Sachs years ago, and due to medical error they were told they were not carriers. Shari subsequently gave birth to Evan Lee, who was a Tay-Sachs baby. Ungerleider explained that she knows of one couple who was informed by Quest Diagnostics that they were not carriers. That couple's son - born five years ago - was also afflicted with Tay-Sachs.
"My understanding is that they knew in 1997 that these mistakes were around," continued Ungerleider. "They felt they were isolated incidents, so there was no reason to alert or alarm people. I guess they [later] realized that their ranges were wrong and they decided to start notifying people about it. And it took them so long to notify people."
"The assignment of Tay-Sachs carrier status is based on statistically derived cutoff levels and therefore is subject to some inherent limitations," Samuels explained. He described how the test provides a range of values for enzyme activity. Patients who test at the upper end of the range are clearly noncarriers. Patients whose enzyme activity falls in the low end of the range, are classified as carriers of the Tay-Sachs gene. For those whose range is in the middle, "there's an overlap between the upper end of the carrier range and the lower range of the noncarrier range and we call that gray zone the inconclusive range," reported Samuels. At the end of 1998 the company decided to interpret the test in a more conservative manner. "We expanded the inconclusive range to make the test more sensitive."
"In fact, we did this analysis in connection with a lawsuit," revealed Samuels. "...It's a settled case. It was settled earlier this year... There was another case earlier in the 90's, 1996 or 1997...and as we began to launch this retesting program we received a third lawsuit."
As a result of this adjustment in ranges for enzyme activity, some patients originally designated as noncarriers now are considered to be "inconclusive". And Quest Diagnostic is therefore recommending retesting of those individuals.
Of the 36,000 tests administered during 1992-98, Samuels estimated that 8,200 individuals would be recommended for retesting. Samuels emphasized, "We expect that 99% of the people recommended for retesting will continue to be [classified as] noncarriers."
"We're just trying to notify patients who were tested by either us or our predecessor companies," informed Samuels. Thus, the laboratories involved include Corning Clinical Laboratories, MetPath, and MetWest in addition to Quest Diagnostics.
"We have been for the past few months actively trying to notify all people recommended for retesting. Three quarters of the people recommended for retesting are in the New York greater metropolitan area, and there are other individuals all over the country," Samuels said.
The notification process began with the company contacting physicians who administered the Tay-Sachs tests. "Initially, starting in early April we began contacting doctors by telephone, then we'd follow it up with mailings, to notify them that we were launching the retesting program and urging them to have patients who were pregnant or considering a pregnancy to be retested immediately," recalled Samuels. "The rate of participation was not satisfactory based just on the doctors notifying their patients."
"We have since supplemented that communication blitz with direct letters to patients and we're now advertising [in newspapers]," Samuels reported. "Our goal at this stage is to make sure we've done everything we can to notify any patient who's recommended for retesting."
"We're doing the confirmation using two separate tests, the leukocyte enzyme test and also DNA testing," explained Samuels.
According to a press release from the company, "Quest Diagnostics will cover the cost of retesting, including office visits, if necessary." The usual cost for both tests is approximately $300.
Testing for genetic diseases is currently done by commercial laboratories such as Quest Diagnostics and Genzyme Genetics as well as academic medical centers. "There is no commercially available FDA approved Tay-Sachs test. So each laboratory develops its own test. So what you'll find is a number of different protocols," revealed Samuels.
Ungerleider strongly emphasized the importance of going to "the appropriate place to get tested....Generic labs don't do proper testing for a couple of reasons," she explained. "They don't do the testing in-house themselves, so it gets sent out to various labs, so it goes through too many hands, which makes more room for error. And they don't necessarily have the appropriate people working there doing the testing."
"Unless they have a geneticist on staff there, labs can't legally say 'this person is a carrier' or 'this person is not a carrier' because there's no one there to interpret it," cautioned Ungerleider. "So unless there's a geneticist on board to determine that, then it's up to the doctor... and there are too many avenues for error there. That's why you're better off going to one place where you can get the [genetic] counseling...It's definitely more expensive, but not any more expensive than having a child with the disease... In this area, I always recommend Mt. Sinai, and UMDNJ Rutgers has a genetic center as well."
"You should be made aware of all the diseases you're at risk for, not just Tay-Sachs," she added. "... because now there are all these other diseases that Ashkenazi Jewish people are able to be tested for."
The National Tay-Sachs and Allied Disease Association has sponsored free testing days for Jewish genetic diseases, and, according to Ungerleider, they are planning another such free genetic testing day at St. Barnabus Medical Center in New Jersey on October 29, 2000.
"Because of the last testing day we did, St. Barnabus ended up getting a very large grant and they opened up a Jewish Genetic Disease Center," informed Ungerleider. "So to kick off the opening we're going to have a Free Testing Day again. They're going to do all the counseling and the blood draws there, and then send the samples to Mt. Sinai where they'll do the testing."
The testing will cover seven genetic diseases commonly found in the Ashkenazi Jewish population: Tay-Sachs, Canavan, Gaucher and Neimann-Pick diseases, Cystic Fibrosis, Bloom Syndrome and Fanconi Anemia. The usual cost of $375 for such screening will be covered by the grant.
Quest Diagnostics has provided a toll-free Hotline, 1-877-806-8175, for questions concerning their retesting program.
The National Tay-Sachs and Allied Disease Association, New York Area, Evan Lee Ungerleider Foundation, can be reached at (212) 431-0431.
© 2000 Miryam Z. Wahrman