27 September 2007
Type 1 Gaucher Disease (GD) is an autosomal recessive condition caused by mutations in the glucocerebrosidase gene. Symptoms are highly variable but may include anaemia, enlarged spleen, frequent infections, bleeding or bruising, and bone disease. Some individuals have symptomatic disease during early childhood, while others may remain asymptomatic throughout life. Enzyme replacement therapy is an effective treatment for affected individuals but is extremely expensive. The carrier frequency for GD is about 6% in Ashkenazi Jews compared to 0.7-0.8% in non-Jewish populations, and the condition has therefore been included in carrier screening programmes available to Ashkenazi Jews in Israel and some other countries.
Writing in the journal JAMA, Zuckerman et al have analysed the outcomes of carrier screening for GD in Israel between 1996 and 2003 [Zuckerman S et al (2007) JAMA 298, 1281-90 (abstract)]. They report that, during this time, 10 Israeli genetic centres screened nearly 29,000 individuals who reported Ashkenazi Jewish descent, identifying 82 carrier couples for Type 1 GD. On the basis of the mutations detected, 70 of these couples were informed that they were at risk of having asymptomatic or mildly affected offspring, and 12 that their offspring would be at moderate risk. In subsequent pregnancies for these couples, there was 76% uptake of prenatal diagnosis, leading to pregnancy termination for 67% of fetuses predicted to be moderately affected and 15% predicted to be asymptomatic or mildly affected. Although information and counselling was available to all couples, not all had access to a clinician expert in GD; in those who did, there were substantially fewer terminations. The discovery of carrier status in parents also had implications for older children born before the screening programme began; although none of these children were symptomatic, some were subsequently tested and found to be homozygous for Type 1 GD mutations.
Comment: The aim of carrier screening is to provide information and choice to couples who are at risk of transmitting severe genetic conditions to their children. Most professional organisations have recommended against population carrier screening for Type 1 GD because of its low penetrance, clinical variability and poor genotype-phenotype correlation, but have fallen short of calling for existing programmes to be stopped, arguing that couples should have the right to decide whether they wish to participate. Zuckerman and colleagues’ paper provides valuable evidence about how couples react to such programmes. Their findings suggest that, rather than empowering couples, screening places them in the position of having to make serious reproductive decisions on the basis of very poor information. The time for careful consideration of the benefits and harms of screening programmes is clearly before they are introduced, not after.