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Study Questions Genetic Screening for Treatable Diseases

TUESDAY Sept. 18, 2007 -- Some Israeli couples with fetuses that tested positive for Gaucher disease, an inherited condition that can range from mild and treatable to severe, chose abortions, raising questions about the use of certain types of genetic screenings, a new study suggests.

The study authors also question the use of genetic screening for other kinds of mild hereditary disorders.

Gaucher disease (GD) includes three diseases caused by deficient activity of a certain enzyme. Common type 1 Gaucher disease often causes no symptoms and is usually not severe and can be treated, the researchers said.

According to the National Gaucher Foundation, the most common symptoms of the disease are enlarged livers and spleens; anemia; reduced platelets that can result in easy bruising and clotting difficulties; bone "infarctions" that can lead to damage to the shoulder or hip joints; and a generalized "demineralization" of the bones, or osteoporosis. This can lead to spontaneous fractures.

Gaucher disease is relatively common in Ashkenazi Jews, who have been offered screening worldwide and in Israel since 1995, according to background information in the study.

But the use of this screening is controversial, because the test does not fully predict the severity of the disease. Even so, some couples decide to abort a fetus if it tests positive for Gaucher disease, the researchers noted in the Sept. 19 issue of the Journal of the American Medical Association.

In the study, a team led by Shachar Zuckerman of Shaare Zedek Medical Center in Jerusalem analyzed data from 10 Israeli medical centers that offered Gaucher disease screening. From January 1995 to March 2003, there were about 28,893 people screened at the centers. Of those, there were 83 GD carrier couples. The GD carrier frequency was 5.7 percent.

There were 82 couples at risk for children with type 1 GD. Seventy of the 82 couples (85 percent) were at risk for asymptomatic or mildly affected children, and 12 of the 82 couples (15 percent) were at risk for moderately affected children, the study found.

Prenatal diagnosis was performed in 68 of 90 (76 percent) pregnancies, and pregnancies were terminated in four of 16 (25 percent) cases of fetuses with Gaucher disease. Of the four aborted fetuses, two were predicted to have asymptomatic, or mild GD, and two were predicted to have moderate disease.

The study found that there were far fewer pregnancy terminations among couples who, in addition to receiving genetic counseling, also had medical counseling with a Gaucher disease expert -- one of 13 (eight percent) of pregnancies, compared with three of three (100 percent) among couples who did not receive medical counseling.

"With respect to the stated goal of carrier screening programs, the main practical outcome of GD screening was a 66 percent reduction in birth prevalence for moderate type 1 GD, for which the estimated frequency is 1 in 27,000, and a 15 percent reduction in the birth prevalence of asymptomatic or mild type 1 GD, for which the estimated frequency is 1 in 1,300. This was achieved through termination of pregnancy of fetuses either treatable or likely to be asymptomatic, and it is debatable whether this represents a true benefit," the study authors wrote.

They noted that the Israeli Medical Geneticists Association has recommended against Gaucher disease screening.

In an accompanying editorial in the journal, Dr. Ernest Beutler, of the Scripps Research Institute in La Jolla, Calif., said, "Not until clinicians and researchers better understand the factors that determine whether a patient homozygous for the N370S (GD) mutation will develop severe disease or none at all will screening for Gaucher disease become useful. Until then, screening for Gaucher disease will likely do more harm than good."

Zuckerman and his colleagues also questioned the use of genetic screening for other mild hereditary conditions.

"Applying the classic carrier screening paradigm to common, low-penetrance disease leads to inevitable dilemmas, and programs offering such screening should determine whether the true goal is knowledge and presymptomatic risk assessment or pregnancy termination of fetuses with a specified genetic status," the researchers wrote.

"Our results suggest that to avoid termination of pregnancies for generally mild conditions, even in a highly educated population, screening programs would require a combination of traditional, nondirective genetic counseling with medical counseling by professionals familiar with the specific diseases," they concluded.

More information

To learn more about Gaucher disease, visit the National Gaucher Foundation.

Posted: September 2007


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