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04/02/2001 - Updated 11:55 AM ET

Cystic fibrosis carrier-testing gains support

By Rita Rubin, USA TODAY

Tammy Stringer never had any reason to give much thought to cystic

fibrosis. As far as she knew, no one in her family ever had it.

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But in a prenatal class during the first trimester of her first

pregnancy, Stringer, 23, learned that she could be tested to see

whether she carries a CF gene mutation. What's one more test? she

figured. " I didn't give it any thought. I said, 'Sure, why not?' "

rs don't have CF, but if both parents are carriers, a child has

a one-in-four chance of being born with the disease. CF causes sticky

mucus to build up in the lungs, pancreas and other organs, leading to

respiratory and digestive complications.

For the most part, only pregnant women with a family history of CF

have been offered carrier screening. But that is about to change.

In the current issue of Genetics in Medicine, the American College of

Medical Genetics (ACMG) has published guidelines for so-called

population-based CF carrier screening: All Caucasians, not just those

with a family history, should be offered the test. Though more than

900 CF mutations have been identified, the ACMG for now recommends

testing for only the 25 most common. The test would identify 80% of

Caucasian CF carriers.

Members of other racial groups are less likely to be carriers, and

scientists have not yet identified all of their common mutations. If

minority members are interested in testing, they should be told of

its limitations, the ACMG says.

Within a year or two, medical geneticists expect population-based

screening for CF carrier status to become standard, making it the

largest-scale DNA testing ever.

Estimated: 10 million carriers

Only 30,000 Americans have CF, so, up to now, relatively few pregnant

women have routinely been offered carrier testing. The Cystic

Fibrosis Foundation estimates that 10 million Americans carry CF

mutations, including as many as one in 25 Caucasians. In most cases,

carriers learn of their status only by having a child with CF.

For years, Jews of Eastern European descent have been routinely

tested to see whether they are Tay-Sachs carriers, regardless of

family history. The same for blacks and sickle cell anemia.

But the larger potential market for CF carrier screening takes the

ethical and practical concerns surrounding such testing to a new

level. " The whole idea of testing pregnant women begs the question of

whether you should keep the baby, " says Carolyn Habbersett, director

of public affairs for the Cystic Fibrosis Foundation.

Wayne Grody, lead author of the ACMG statement, acknowledges

that " the ultimate goal is to have fewer patients with CF, since we

don't have a cure right now. "

Today, average life expectancy for a person with CF is 32 years. Some

live far longer, some far less.

" Tay-Sachs is so horrible, " says Grody, a medical geneticist at

UCLA. " There's no treatment. They die by age 2. People don't have too

much trouble about the concept of terminating those fetuses.

" CF can be a somewhat variable disease. Some patients are only mildly

affected. "

Population-based screening is cost-effective only if most parents of

affected fetuses terminate the pregnancies, says Asch, a health

economist at the University of Pennsylvania.

" If you're not going to do anything differently, why get the test in

the first place? " Asch asks.

A simple $200 test

Genzyme, of Framingham, Mass., a leading provider of CF carrier

testing, says it charges about $200 per test. Centers that offer

population-based screening say health plans generally have been

covering it. The test is simple to do, requiring only a blood sample

or a cheek swab. Generally, only if both parents test positive do

they need to have a lengthy discussion with a genetics counselor.

Witt, a medical geneticist at Kaiser Permanente of Northern

California, says it's far less costly to perform screening in-house,

as his plan does.

Since November 1999, Witt's health plan has been offering CF carrier

testing to all pregnant women who are at least part Caucasian or

whose partners are.

Nearly 20,000 women have been tested, including Stringer. If a woman

is found to be a carrier, her partner is tested. In only 19 cases

have both parents turned out to be carriers, Witt says.

Some of the 19 mothers miscarried before amniocentesis could be

performed to determine if their fetus had CF. Of the remaining

pregnancies, amniocentesis so far has identified only one fetus with

CF, and the parents terminated the pregnancy, he says.

" Just because you have prenatal testing doesn't mean you're going to

terminate, " Witt adds. " For some people, the information is important

so they can plan. "

Once pregnant women learn that CF carrier screening is available,

it's hard to pass it up, says genetics counselor Elena Ashkinadze of

St. Barnabas Medical Center in Livingston, N.J., which offers testing

to those with no family history of the disease.

" I think the main reason people have testing is because this

information has been presented to them, " she says. " Now that it's

presented to them, it's kind of raised a level of anxiety, and this

is a way to reduce this anxiety. "

Pilot studies, in which pregnant women were offered free screening

for research purposes, found that as many as 80% of those with no

family history opted for it.

" That's a very expensive way of delivering reassurance, " Asch says.

Testing actually raised Stringer's anxiety, at least temporarily. She

was found to be a carrier. " Our genetics counselor was awesome, " says

Stringer, of Dinuba, Calif. " She said, 'None of this means anything

unless your husband is a carrier.' "

Her husband, , 27, went for testing on his next day off from his

job as a youth pastor. A couple of weeks later, the Stringers learned

that he, too, is a carrier.

The couple then decided to have amniocentesis, although they say they

would never have ended the pregnancy.

" If the baby had CF, I wanted to have the time to prepare, to get

educated, to educate our friends and family, " she says.

Three weeks after the amnio, the Stringers finally learned that their

daughter was only a carrier. a Keersten is now 8 months old

and healthy. But learning that they are CF carriers cemented the

couple's decision to have only one child, Tammy Stringer says.

" I don't regret being tested at all, " she says.

Genzyme Study Finds that Testing for More Gene Mutations Could

Improve Cystic Fibrosis Screening

Date: May 21, 2001

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Genzyme General (Nasdaq: GENZ) reported that a study by its

scientists, published today in Genetics in Medicine, concluded that

cystic fibrosis screening could be improved by using a test that

includes a broad range of gene mutations. The journal is the official

publication of the American College of Medical Genetics (ACMG), the

professional organization for clinical geneticists in the United

States.

The finding comes in the wake of a recommendation by the ACMG that

couples planning a pregnancy or seeking prenatal care be offered DNA

testing to screen for common mutations in the cystic fibrosis gene.

Such " carrier testing " attempts to identify those who do not manifest

the disease but who carry a genetic mutation that may be passed on to

their offspring. Should both parents carry a genetic mutation

associated with cystic fibrosis, there is a 25 percent chance that

each of their children will be born with the disease. More than 10

million Americans are cystic fibrosis carriers. The disease occurs

with the greatest frequency among Caucasians.

More than 900 mutations in the cystic fibrosis transmembrane

regulator (CFTR) gene have been identified since the gene was

discovered in 1989. Screening for all 900 would be neither practical

nor cost-effective, leading to considerable debate over which

mutations should be included in a core testing panel.

Current guidelines recommend that cystic fibrosis tests screen for 25

mutations known to occur with a frequency of 0.1 percent or greater

in the U.S. population.

However, in the most comprehensive analysis to date, Genzyme

researchers found 64 mutations that occur with this frequency. In

their study of 2,920 patients with cystic fibrosis across all 50

states, the researchers concluded that an expanded DNA test that

included these 64 mutations would detect more cystic fibrosis

carriers than would the 25-mutation test.

Specifically, in a population as diverse as the one studied, a 64-

mutation test would have detected 81.4 percent of all cystic fibrosis

carriers whereas the 25-mutation test would have detected only 75.3

percent. If these tests were used for general population carrier

screening, the recommended 25-mutation panel would miss 1 in 17

carriers compared with the 64-mutation panel. Missing 1 in 17

carriers would result in 1 in 1,156 unexpected cystic fibrosis

births. This is relevant in the context of millions of U.S. births

each year. In the Hispanic and African-American populations, the

recommended 25-mutation panel would miss 1 in 7 and 1 in 11 carriers,

respectively, compared with the 64-mutation panel.

" As the ACMG recommendation for universal CF screening is implemented

over the next few years, we anticipate continued discussion about the

appropriate core panel that should be used to screen for a disease

that involves such a large number of potential gene mutations, " said

Mara Aspinall, president of Genzyme Genetics. " This study shows that

by expanding the standard CF testing panel modestly to include at

least 64 mutations, you can significantly increase detection of CF

carriers and still offer a practical, cost-effective test. We look

forward to working with the ACMG and other professional societies to

incorporate this research into future guidelines for CF carrier

tests. "

Genzyme Genetics, the genetic testing services unit of Genzyme

General, offers a DNA test that screens for 87 cystic fibrosis gene

mutations, far more than any other laboratory. Genzyme's CF87® test

screens for the 64 most common mutations, along with 23 rarer

mutations. By screening for this broader range of mutations, the CF87

test increases testing sensitivity in the ethnically diverse U.S.

population. Specifically, a 25-mutation panel would miss 6 of every

100 carriers that would be detected by the CF87 test. The 25-mutation

panel would miss 3 of every 1,000 carrier couples that would be

detected with the CF87 test.

Cystic fibrosis is the most common fatal hereditary disease among

Caucasians in the United States, with a median life expectancy for CF

patients of 32 years. Cystic fibrosis is caused by a defective gene

that affects multiple aspects of cellular function. The most

debilitating consequences of the disease occur in the lungs of

patients, where abnormally thick, sticky mucus clogs the airways,

leading to fatal lung infections.

Genzyme Genetics, a business unit of Genzyme General, is a leader in

providing high quality genetic testing and counseling services to

health care professionals and their patients, performing nearly

400,000 genetic tests a year. Genzyme Genetics is the largest

provider of cystic fibrosis screening in the world.

Genzyme General develops and markets therapeutic products and

diagnostic products and services. Genzyme General has four

therapeutic products on the market and a strong pipeline of products

in development focused on the treatment of genetic disorders and

other chronic debilitating diseases with well-defined patient

populations. Genzyme General is a division of the biotechnology

company Genzyme Corporation.

This press release contains forward-looking statements based on

management's current expectations, including statements about:

estimates concerning the incidence of cystic fibrosis and the cystic

fibrosis patient population; the potential adoption by health care

practitioners of the ACMG recommendations for cystic fibrosis

testing; the expected benefits of the use of the specific cystic

fibrosis test panel developed by Genzyme; and the estimated number of

genetic tests performed by Genzyme each year. Actual results may

materially differ due to numerous factors, including without

limitation: the accuracy of Genzyme's information concerning the

cystic fibrosis patient population and the incidence of the disease;

the willingness of relevant patient populations to undergo cystic

fibrosis screening; acceptance of new cystic fibrosis screening tests

for reimbursement by third party payors and the extent of such

coverage; the level of use of Genzyme's research efforts by

professional societies in developing practice guidelines; the impact

of the lack of an effective treatment for cystic fibrosis on

decisions as to whether to screen for cystic fibrosis; market

acceptance of Genzyme's cystic fibrosis tests; the competitive

environment in the cystic fibrosis testing market and the overall

genetic testing market; and the risks and uncertainties described in

reports filed by Genzyme Corporation with the Securities and Exchange

Commission under the Securities Exchange Act of 1934, as amended,

including without limitation Exhibit 99.2 to Genzyme's 2000 Annual

Report on Form 10-K, as amended. Genzyme General Division common

stock is a series of common stock of Genzyme Corporation. Therefore,

holders of Genzyme General Division common stock are subject to all

of the risks and uncertainties described in the aforementioned

reports.

Genzyme® and CF87® are registered trademarks of Genzyme Corporation.

All rights are reserved.

Note to editors: The ACMG recommendation for population-based cystic

fibrosis carrier screening was published in the March/April 2001

issue of Genetics in Medicine (Vol. 3 No. 2).

Please call Genzyme's corporate communications department at 1-617-

252-7570 for additional information.

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