Researchers have identified the gene that causes an incurable disease affecting only a few thousand people around the world. But the news is causing ripples of excitement among geneticists everywhere.
By Judy Siegel-Itzkovich
Familial Dysautonomia (FD) is a degenerative and fatal disorder that solely affects people of Ashkenazi (European) Jewish origin. Also known as Reilly-Day Syndrome (named for the two pediatricians who first identified it in 1949), FD is as common among European Jews as the similarly devastating Tay-Sachs disease, but is much less well-known.
FD leads to poor development and degeneration of the sensory and autonomic nervous systems those which are associated with involuntary functions such as swallowing, digestion, temperature and blood pressure. The symptoms include abnormal sweating, hypertension, vomiting, frequent pneumonia, speech and motor problems, irregular blood pressure, red and puffy hands, scoliosis, feeding and sucking difficulties in infants, gastrointestinal dysfunction and inappropriate perception of heat, pain and taste. Only half the patients survive their 30th birthday. The most distinctive clinical sign is the lack of overflow tears with emotional crying (although it is normal for some children not to have tearing until seven months of age). There is no cure for the disorder, but there are various treatments aimed at alleviating symptoms. For example, patients use artificial tear solution to protect the eyes and medications to avoid vomiting and control blood pressure. Children must be fed carefully to prevent choking or developing aspiration pneumonia.
One out of every 32 Ashkenazi Jews carries the recessive gene, which is located on the long arm of the ninth chromosome. If the gene is present in both parents, there is a one-in-four risk of their child being born with the disorder. If only one parent bears the mutated gene, their children would be symptom-less carriers.
The gene was jointly discovered after many years of research by Dr. Ana Blumenfeld and Dr. Channa Maayan of Hadassah-University Hospital on Mount Scopus in Jerusalem, Dr. James Gusella and Dr. Susan Slaugenhaupt from Massachusetts General Hospital and Harvard Medical School among other colleagues. (Maayan directs Israel's National FD Center, which treats most of the surviving patients in the country.) The discovery was published in February on the Internet site of the American Journal of Human Genetics and in March in its printed edition. The article has elicited interest among scientists around the world because the finding is expected to revolutionize genetic testing and eventual treatment for this and other types of devastating neurological disorders.
"The discovery also opens wide the doors for experimentation that will hopefully someday provide a cure," Blumenfeld explains. "This will benefit not only Jews, but the general population who suffer from numerous types of hereditary autonomic and sensory neuropathy disorders related to FD. It is a disease model for the others; these are disorders of the involuntary nerves controlling digestion and other functions a person cannot control. These destroy nerve cells in infants and children, and as we do not know how to grow new nerves, genetic therapy is not yet possible. However, better treatment could result if we find ways to prevent the deterioration of the nerve cells at a young age," she continues.
There are 113 surviving FD patients in Israel, and one of them is the 16-year-old son of Dr. Anat Shiran, a physician in Haifa and head of the Israel FD Association. She was overjoyed by the gene discovery, even though it will not offer immediate help to her son. "Day-to-day care of FD children is very difficult," Shiran says, "with the burden falling mostly on the parents, along with the devoted nurses and doctors who work in outpatient and inpatient facilities. Parents of children born with FD can now have further pregnancies screened."
Until now, blood tests were taken only of members of families in which at least one living individual has been diagnosed with FD. In a procedure called linkage analysis, the lab also took a sample from the affected relative and then compared his or her genetic profile with that of those who want to know their FD status. But thanks to the gene discovery, couples of Ashkenazi origin are now able to go for screening of the gene at Blumenfeld's laboratory on Mount Scopus. The test is free for those who have a blood relative with the disease. Similar tests may soon become available at other laboratories, as well as at Dor Yesharim (the Committee for Prevention of Jewish Diseases), an Orthodox Jewish organization based in New York that performs genetic screening on young couples who wish to get married.