Avoiding a life of struggle and suffering

Familial dysautonomia, a rare and terrible Ashkenazi genetic disease, is now preventable.

child doctor 248.88 courteys (photo credit: Courtesy)
child doctor 248.88 courteys
(photo credit: Courtesy)
You wouldn't wish familial dysautonomia (FD) on your worst enemy. This rare and incurable genetic disease - which affects mainly Jews of Ashkenazi origin and is also known as Riley-Day syndrome for the doctors who first described it in 1949 - causes almost every major bodily system to malfunction chronically, and most victims also suffer sudden acute attacks. Almost 800 people have been diagnosed with it in the past six decades, with 380 around the world - 136 in Israel - currently living with it. A few decades ago, most patients died by the age of five. Yet better understanding of the disorder and the identification of the defective gene that causes it in 2001 - as well as therapies that keep patients alive but do not cure them - have extended life expectancies and improved quality of life. Today, the annual mortality rate is only 2%, and half of all Israeli FD patients are over 17. One Israeli with FD is a 52year-old grandfather, while another has a master's degree and has written a book. But nevertheless, it is a horrible ailment. Victims are constantly aware of the possibility of impending death. The "mother" of Israeli FD patients is Prof. Channa Maayan, a specialist in children's lung diseases who heads one of the world's two FD centers. Hers is at Hadassah University Medical Center on Jerusalem's Mount Scopus, while the other is at New York University. Her cramped center on the ground floor of the Mount Scopus hospital is funded solely by the Dysautonomia Foundation in the US ( established by patients' parents) and much-needed donations, rather than by the Health Ministry and the health funds, which seem to take the Israeli FD Center for granted. Some come to Jerusalem from as far as England to get help. The center was founded 28 years ago by pediatric lung expert Prof. Simon Gottfried, the hospital's retired head of pediatrics, when there were only about 20 FD patients in the world. He persuaded Maayan, who returned to Israel from research into sleep apnea at Massachusetts General Hospital, to join the center. Today it has another physician besides Maayan, a nurse, dietitian, social worker, educational adviser, secretary, physiotherapist, psychologist, coordinator and volunteers ( most of them part time). Maayan - who was born to a Hadassah nurse at the hospital where she works - is on duty 24 hours a day, 365 days a year. She and her small staff publish their office, cellular and home phone numbers in the booklet they give patients, who call at all hours. They often take patients on trips around the country. Maayan displays photos of her patients on her computer as if they were family. One out of every 30 Jews of Ashkenazi origin (including those with only one Ashkenazi parent) carries the defective gene, and if the Jews are of Polish origin, the rate is one in 18. Apparently, the defect appeared in Polish Jews hundreds of years ago, and inbreeding led to its spread. FD affects the development and survival of certain nerve cells, specifically those of the sensory and autonomic nervous systems (hence its name). It also causes severe gastrointestinal, cardiac, pulmonary, orthopedic, renal and ophthalmological problems. Although there are wide variations in severity, sufferers face tremendous challenges from birth, including frequent hospitalizations, major surgery and daily medical therapies. "I used to work with cystic fibrosis and severe asthma patients," recalls Maayan, "but this is the worst. It is a life of suffering." The clearest FD symptoms are the inability to produce overflowing tears and reduced sensitivity to pain. But these symptoms are the least of it. Children lack the most basic reflexes. They can't control their blood pressure and heart rates, which swing dangerously. They lack the ability to suck from birth and subsequently to swallow properly. Because food often ends up in the trachea and lungs instead of the esophagus and stomach, they are prone to aspiration pneumonia, so most have a gastric feeding tube. Children are usually short, have red, puffy hands, crooked teeth and an asymmetrical face. Some rub their nose so much that part of it wears down. They get bone fractures without realizing it due to osteoporosis and have an unstable gait, Maayan notes. Some need to undergo spinal fusion, while many need antibiotics, ventilation and physiotherapy. There are as yet no specific drugs that target FD, but it is hoped that research will lead to an understanding of exactly what causes the symptoms. In that case, some treatment could follow. FD also causes a mysterious syndrome called "autonomic crisis" in which patients experience extreme swings in blood pressure and heart rate, along with nausea, kidney failure, dramatic personality changes and a complete shutdown of the digestive system. Once FD patients go into crisis, they can't participate in any normal activity for hours or days afterward, and may require hospitalization, sedation and hydration until the crisis abates. Girls' menstrual cycles may disappear. Patients may throw objects in anger. Because they lack tears, their corneas develop scars, and eye drops are constantly needed. They are often hypersensitive to anesthesia, have blotches on their skin, decreased muscle tone and sweat excessively. But most of them have normal or above-average IQs and warm personalities. "God gave them an extra soul. They are fantastic people who are easy to love, even though they look different. Some suffer from depression, but I don't know of any who have committed suicide," the center director adds. Maayan participated in the effort that led to the discovery of the recessive IKBKAP gene whose mutation in FD patients causes the absence of IKAP protein, leading to the signs and symptoms. The work was headed by Dr. Susan Slaugenhaupt of Boston and published in the American Journal of Human Genetics nearly eight years ago. With the discovery of the gene, young men and women can know if they are carriers. Religious Jews of Ashkenazi origin who underwent gene testing at Dor Yesharim - the genetic defect testing and registry organization - since 2001 will know if they are compatible with others of the same background. But if they were tested before 2001, they need a re-test. Fortunately, a few months ago the Health Ministry added a blood test for screening FD carriers to the basket of service, so all Jews of Ashkenazi origin can now ask to be tested at no cost, says Prof. Yoel Zlotogora, the ministry's genetic testing expert. If two single Orthodox Jews of Ashkenazi origin learn from Dor Yesharim that they are not compatible due to FD (the organization does not identify carriers, but tells those registered whether their match is genetically healthy), they may nevertheless marry. There is a 25% risk in each pregnancy that the fetus will have FD. Today, embryos produced by in-vitro fertilization (IVF) can undergo pre-implantation diagnosis to discover whether they inherited FD; such embryos are not implanted. When a fetus is produced by two carriers, it may also be aborted. But despite the ability to prevent the birth of all FD babies, three were born in Israel in the past year, and 33 since 2001. A foster family is being sought for one FD baby who is hospitalized at Hadassah. This is unnecessary and needless suffering, says Maayan. But most Jews of Ashkenazi origin have never heard of FD, let alone of the need to ask for a blood test for it before marriage. "The number of FD babies born is seven or eight per year. It has fallen, but the number can be 0," Maayan insists. Zlotogora concedes that the absence of a public education campaign is partially responsible for the birth of FD babies, but says that such an effort will soon be carried out now that the test is in the basket of health services. It is not only the physical and emotional conditions of 138 patients that keep Maayan and her staff busy, but also National Insurance Institute "red tape." Patients are recognized as having a 100% disability, but Maayan says there have been many cases in which patients had to present documents every year "even though their disease will never go away." The Jerusalem Post contacted the NII and Irit Feldman, the official in charge of quality control, looked into the matter. "We know that FD is a very serious genetic disease, but regulations prevented us from automatically giving an exemption from having to present documents every year." But a few months ago, it was decided to relieve these unfortunate patients of such red tape. Feldman has now instructed the NII nurse to deal with all cases in which FD patients are mistakenly asked to present documents to get their NII allotments. The center coordinates treatment in other hospitals for patients who cannot get to Hadassah when they suffer an acute attack. It also lends equipment to patients, holds workshops and lectures to medical specialists around Israel and even abroad about the complicated disease. Stem cells are being considered as a possible treatment. Hadassah researchers are also attempting to create a mouse model for FD that could help find the enzyme that devastates patients' neurological systems. "Working with FD patients is frustrating," concludes Maayan, "but we get satisfaction from helping them. The most important aims now are to prevent the birth of babies with FD and finding a cure for those who already have it." More information about Hadassah's National Familial Dysautonomia Center can be obtained from the Hadassah Web site at www.hadassah.org.il. Contributions can be sent to the center at POB 24035, Jerusalem 91240.