Physicians at Hadassah University Hospital in Ein Kerem have discovered a genetic disease heretofore unknown in the scientific literature, and also succeeded in treating it.
The disease, which has yet to acquire a formal name and is known as TPP2 deficiency, is a blood disease in which a particular protein deficiency causes the immune system to attack itself, and leads to accelerated cell aging and severe side effects that cause death. It is most common in populations in which close relatives marry each other.
The doctors first encountered the illness a decade ago but could not diagnose it. In recent years, however, a hospital team succeeded in defining the disease and characterizing it in terms of its clinical presentation, genetics, and immune cell function. A report on the research, which appeared last year in Blood, the journal of the American Society of Hematology, was just chosen as one of the journal’s top 10 stories for 2015.
The journey of discovery began over 10 years ago when a 21-month-old boy from Nablus was brought to Hadassah suffering from severe symptoms of an unexplained malfunction of the immune system. His older sister had died of the same syndrome when she was three. “The Palestinian hospital could not diagnose the disease, and we didn’t know at first what it was either,” explained Dr. Polina Stepensky, head of the Hadassah’s pediatric hemato-oncology and bone marrow transplantation department. “When the symptoms appeared in the sister the doctors tried various treatments but they didn’t know exactly what the diagnosis was and it didn’t help and she died.”
When the little boy, started exhibiting the same preliminary symptoms, “His mother was the first to understand that it was apparently the same illness and it was liable to end the same way,” Stepensky said. The mother therefore brought the child to Hadassah.
As part of the diagnostic process, Stepensky and Prof. Orly Elpeleg of Hadassah’s genetic research department, used an innovative technique to create a genetic sequence of the boy and his family, and discovered a damaged gene in the family that expressed itself in a deficiency of the protein TPP2. With the help of German researchers, the mechanism of the disease was characterized, as well as the way in which the TPP2 is involved in the proper functioning of the immune system’s cells.
The protein helps identify foreign proteins that threaten the immune system and its absence leads to a decrease in hemoglobin and other blood indicators, and to repeated infections, some life-threatening. But although the disease destroys blood cells, normal blood tests will not detect it; diagnosis requires genetic testing.
Ever since the Human Genome Project was completed in 2006, followed by technological developments that allowed for relatively easy and inexpensive genetic sequencing, medical and life science researchers have been better able to define and understand various biological mechanisms. “We actually discovered a new mechanism of the immune system, a previously unknown path that leads to premature aging of the immune system, which both allowed us to diagnose this disease and will also help us better understand the whole system,” Stepensky said.
During 2014, when the boy who started it all turned 12, after years of treatment with immunosuppressive drugs, doctors decided that the most effective treatment would be a stem-cell transplant to rejuvenate his immune system. He got the transplant from the bone marrow of his healthy seven-year-old sister and now seems to be well.