La Jolla scientists have identified the second major genetic defect that causes Gaucher's disease, a debilitating, inherited disorder that is most common among Jews of European descent.

The discovery makes it possible for the first time to identify carriers of Gaucher's disease--an estimated one of every 12 Ashkenazic Jews--with full confidence that virtually all affected individuals will be identified. It also makes possible effective prenatal screening.

Researchers at the National Institutes of Health reported in 1988 that they had identified the genetic defect responsible for nearly 75% of the cases of Gaucher's (pronounced go-SHAYS), which affects as many as 15,000 Americans. Researchers have identified at least 14 other mutations in the same gene, but each of those accounts for only a fraction of a percent of victims.

Hematologist Ernest Beutler and his colleagues at the Scripps Research Institute report today in the Proceedings of the National Academy of Sciences that they have identified another defect, in the same gene, that accounts for most of the remaining 25% of the cases.

Although the discovery makes prenatal testing possible, the decision to abort a fetus with the disorder will be ethically difficult--and most likely controversial--because it is not yet possible to predict the severity of the disorder in a child.

Nonetheless, the discovery is "very significant" even if the parents do not choose an abortion, said family practitioner Dr. Robin Berman, medical director of the National Gaucher Foundation. "We can detect people who will be affected at a much earlier stage and allow them to get treatment before they have any bad symptoms of the disorder. That's extremely valuable."

Gaucher's is characterized by a severely enlarged liver or spleen, anemia, bleeding, significant bone and joint pain, fatigue, and orthopedic complications, such as repeated fractures and bone erosion.

Its severity varies widely. In some people, it is very mild and causes few problems. In the most severe form, the affected individual typically dies in the womb or in the first year of life. Typically, the later in life the disorder strikes, the less severe it is.

The disorder is caused by abnormalities in an enzyme, called glucocerebrosidase, that normally degrades a fatty compound called glucocerebroside. Because it is not destroyed, the fatty compound accumulates in the liver, bone marrow and spleen, where it is toxic.