In September, New York University Medical Center will become the first medical facility in the country to offer Ashkenazic Jewish couples tests for 16 inheritable genetic diseases, an expansion from the nine tests it offered until a year ago. Welcomed by some in the medical community as an advance in patient care, the move is prompting others to ask whether patients are equipped to make the proper choices, and whether funds for screening for some of the rarer diseases may not be better allocated elsewhere.
“We decided to add the tests, because they are available and when we ask our patients they indicate that they want more testing,” said Dr. Harry Ostrer, director of NYU’s Human Genetics Program, the department that performs the screening.
Across the country there are a handful of sites and commercial labs that offer tests for genetic disorders that are overrepresented among Ashkenazic Jews. To date, they offer anywhere from four to 11 tests for disorders that include such severely debilitating and fatal diseases as Tay-Sachs, Canavan and familial dysautonomia.
When NYU first began expanding its panel of nine in September 2004, it added tests for Fragile X syndrome, a disorder that causes mild to severe mental impairment. Then, early this year, screening was added for glycogen storage disease, or GSD, a disorder in which the body is unable to break down stored sugars, causing blood sugar to drop to dangerously low levels. Five more tests are being added over the course of the summer.
“Whatever testing is being done, it is crucial that patients get the information on the diseases they are being tested for, so they can make an informed decision on whether they want to be tested,” stressed Kelly Ormond, president of the National Society of Genetic Counselors. Her concern was echoed by other medical professionals, some of whom seemed surprised by the new tests NYU is adding.
Dr. Adele Schneider, director of the Victor Center for Jewish Genetic Diseases at the Albert Einstein Medical Center in Philadelphia, one of the few centers in the country dedicated to both screening and community education, added that obstetricians may not be familiar with the diseases for which they are screening patients.
“I have no problem with testing people,” she said, but “patients should know what they are being tested for. I don’t agree with simply checking off a panel of some 20 diseases when people don’t understand what tests are being done and the implications of a positive result. Genetic counseling is very important.”
NYU offers genetic counseling to all patients who come for screening, noted Ostrer, adding that at his center, increased testing is largely consumer driven. “It is the patients who ask, ‘If these tests are available, why aren’t you offering it to us?’ I don’t disagree with them. Why should we hold back?”
The five diseases for which NYU is adding tests this summer are familial hyperinsulinism, maple syrup urine disease, dihydrolipoamide dehydrogenase deficiency and two forms of Usher syndrome. Hyperinsulinism, like GSD, leads to dangerous dips in blood sugar, but in this disorder the cause is an enlarged pancreas in the newborn that puts out too much of the sugar-digesting compound insulin. Maple syrup urine disease (MSUD) and dihydrolipoamide dehydrogenase deficiency are both metabolic diseases that may put a newborn into a coma. A child with Usher syndrome is born deaf and becomes blind during the first 10 years of its life.
Test costs and allocation of funds are a second major concern, especially at centers that subsidize screening. Schneider of the Victor Center, which provides discounts for the eight tests it offers, pointed out that although more common among Ashkenazic Jews, the added diseases are much less frequent than some of the diseases already being tested for. “It’s expensive and chances for a positive are very, very low,” she noted, adding that if caught immediately, the diseases are not necessarily life threatening. In the state of Pennsylvania, for example, all newborns are screened for MSUD and deafness, and with GSD and hyperinsulinism “blood sugar drops so fast you would know right away,” she said. Nevertheless, in the information it provides patients, the Victor Center includes MSUD and GSD.
“It’s a tough decision,” acknowledged Dr. Ruth Kornreich, co-director of the Genetic Testing Laboratory at Mount Sinai Medical Center in New York City. “Cost is definitely an issue. Something like GSD can be managed somewhat, but on the other hand, a couple with a child with one of these debilitating diseases say it should be screened.”
Mount Sinai, whose Center for Jewish Genetic Diseases is the oldest such center in the United States, screens for 11 diseases, including GSD and MSUD. In the fall, Usher syndrome will be added to the group, said Kornreich, and eventually so will hyperinsulinism and dihyrdolipoamide dehydrogenase deficiency. “Adding tests is usually a joint decision between counselors, doctors and the lab,” she explained. “I think we are doing more good than harm. People definitely want to be screened.”
Centers usually decide which diseases to screen based on four factors: disease frequency in the population, severity of the disease, accuracy of tests and availability of treatment for the disease, explained Ormond.
A carrier frequency of at least one in 100, many experts agreed, is a general criterion. Carrier frequency refers to the chance that a healthy person may carry an altered or mutated gene for a disease. Each person inherits two genes — one from each parent — for almost every bodily trait. Sometimes a mutation in only one of the pair causes illness, but with other traits, a person inheriting one normal gene and one mutated gene will be perfectly healthy, but he or she has become a carrier. When that person has a child with another carrier, there is a 25% chance that the child will inherit both mutated genes and become ill.
With the exception of Fragile X, the genetic diseases for which Ashkenazic couples are being tested are all classified as recessive genetic disorders, and most studies have shown that they are present in the Ashkenazic population at a carrier frequency of at least one in 100.
“But it’s not just cost and frequency. It is also what can be done for people in terms of treatment,” commented Dr. Ronald Bachman, chief of the genetics department at Kaiser Permanente in Oakland, Calif., a nonprofit HMO on the West Coast that funds research and provides comprehensive care. Kaiser screens for only four disorders, Bachman said, “because we don’t have an infinite budget.” Noting that some commercial labs charge up to $3,000 for a panel of tests, he went on to speculate whether some increased testing didn’t have pecuniary motives, as well.
In contrast to the recessive disorders, testing positive for Fragile X may also have consequences for the adults screened, raising more questions on the repercussions of testing. “It has vast implications for the family,” Schneider said. A woman who tests positive is at risk for premature menopause, she added, and a man is at risk for developing FXTAS, a progressive neurological disorder. At NYU, however, Ostrer said, only women are tested for Fragile X, because it is a condition linked to the gender-defining X chromosome. Women who test positive then receive counseling on how they themselves might be affected.
“We see ourselves as empowering patients to make decisions. We provide knowledge and help them make informed decisions,” Ostrer said. “There are other tests we are considering adding, but I think we are getting to the bottom of the well for the moment.”