A number of couples in Israel were told their fetuses screened positive for Gaucher’s disease and decided to terminate their pregnancies. Gaucher’s disease ranges from mild and very treatable to severe. An article in the September 19 issue of the Journal of the American Medical Association (JAMA) puts forward a number of questions regarding the appropriateness of some types of genetic screenings.
The authors explain “Carrier screening can reduce the burden of genetic disease, especially in populations in which specific diseases are common. Although generally performed for severe, untreatable disorders, carrier screening for less serious yet prevalent conditions is also possible, but there is little information on its implications, even though it is likely to become more common.”
Gaucher’s disease (GD) is much more common among Ashkenazi Jews compared to other populations. GD includes three diseases, they are all due to deficient activity of a type of enzyme (glucocerebrosidase), leading to an accumulation of its substrate, the fatty substance glucocerebroside (glucosylceramide). A person with Gauther’s disease may have an enlarged spleen and liver, malformation of the liver, skeletal disorders and painful bone lesions, serious neurologic complications, swelling of lymph nodes and sometimes adjacent joints, a brownish tint to the skin, anemia, distended abdomen, and low blood platelets. In more severe cases the patient is also more susceptible to infection. A French doctor, Philippe Gaucher, originally described the disease, hence its name.
Screening people for GD is controversial because, for example, type 1 GD usually has no symptoms; it is not severe and is completely treatable. The problem is that carrier screening for GD does not tell you how severe the GD is. Since 1995 Ashkenazi Jews have been offered screening globally and in Israel.
Shachar Zuckerman, M.Sc., Shaare Zedek Medical Center, Jerusalem, Israel, and team looked at various aspects of GD screening in Israel. They focused on GD screening’s scope, the process itself and outcomes. They received data from ten genetic centers in Israel – the data included information on various individuals who had been screened for GD, how many carriers were identified, how many carrier couples were identified, and the mutations identified within these couples for the period January 1995 – March 2003. Telephone interviews took place with carrier couples during the period of January 2003 to August 2004.
83 carrier couples were identified out of about 28,893 people who were screened. The authors said GD carrier frequency was 5.7%. 82 couples were considered at risk of giving birth to children with type 1 GD. Of the 82 couples, seventy were at risk for mildly affected or asymptomatic offspring, and 12 of the 82 couples were at risk for moderately affected offspring.
Out of 90 pregnancies, prenatal diagnoses were performed in 68 (76%). Terminations (of pregnancy) were carried out in 4 out of 16 (25%) of fetuses with GD – two fetuses were predicted to have asymptomatic or mild GD, while 2 fetuses were predicted to have moderate GD. The researchers report that among couples who had medical counseling with a GD expert, the number of terminations was significantly lower – 8% of couples who had both genetic counseling and medical counseling with a GD expert terminated, compared to 100% of couples who had no medical counseling with a GD expert.
The authors wrote “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. 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. 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.”
JAMA. 2007;298(11):1281-1290
Written by: Christian Nordqvist