The rare disease was discovered by an international group of researchers headed by Israelis at Sheba Medical Center.
A rare genetic disease that weakens the immune system of children has been discovered among Arab children by an international group of researchers headed by Israelis at Sheba Medical Center at Tel Hashomer.
Information on the discovery of the “orphan disease” (suffered by a relatively small group) was published Thursday morning in the prestigious New England Journal of Medicine.
What began as a clinical observation of a unique phenotype in sick patients has finally been concluded by using advanced genetic and molecular assays to discover the novel disease, said Dr. Raz Somech at the Safra Children’s Hospital at Sheba. He and some two dozen researchers, including Dr.
Christoph Klein, director of Dr. von Hauner University Children’s Hospital in Munich and Bill Gahl of the US National Institutes of Health in Bethesda, Maryland, worked on it.
They observed that the seven affected children suffered from life-threatening infections during the first two years of their lives; their research led to the discovery of an unusual bone marrow malfunction due to mutations in a gene named VPS45 (Vacuolar Protein Sorting 45) as the cause of the disease, which they called congenital neutrophil defect syndrome.
It is estimated that there are dozens of such cases in the Palestinian Authority; none has yet been found among Israeli Arabs.
Five of the children studied were Palestinian Arabs treated at Sheba, while two were Moroccan Arabs treated in Munich. Some of them have already died. All of the children are the result of consanguinity – inbreeding of first cousins – and their illness could have been prevented if their parents had not married, Somech told The Jerusalem Post on Wednesday.
No Jews have been identified with the syndrome, but Somech said that “now we will be able to look. It is a rare disease, but because of consanguinity in this region, we are likely to see many more cases than in other countries.”
In addition to the inbreeding problem, few Arab women agree to undergo abortions.
The replacement of stem cells could successfully treat it, but since there is only a small database of Arab tissue types because few donate such samples, it is unlikely that compatible tissue could be found.
No suitable donors were found in the small Arab tissue type registry at Hadassah-University Medical Center in Jerusalem’s Ein Kerem, Somech said.
If the victims of the disease were Jewish children, it is likely that they could be successfully treated, as there are hundreds of thousands of Jews who undergo voluntary tissue testing so a compatible donor could be found, he added.
The Sheba team are now considering a different – biological – treatment that could prevent the need for bone marrow transplantation for the children who lack a healthy gene.
Children with orphan diseases are at a disadvantage in many ways. They are taken from one doctor to the next in the hope of a treatment or cure being found. In addition, drug companies are very reluctant to invest huge sums to develop treatments when only a small number of patients are involved.
However, genetic research can identify such diseases, and such work can contribute to the advancement of modern medicine, because the examination of these children can supply insights into fundamental principles of biology.
The authors of the paper wrote that the gene VPS45 has several functions in blood cells – it is responsible for membrane transport, for the vitality of the cells and their migration characteristics.
“On the one hand, the identification of this disease and the discovery of its molecular mechanism creates a justified hope for affected patients, as young patients can now receive blood stem cell transplantation earlier” if suitable donors were available.
On the other hand, this research illustrates the importance of new signalling pathways that can possibly influence the therapy of the future – not only for children with rare diseases, but also for younger and older patients with common diseases.
Sheba was been recently acknowledged as a “Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency”– which is the worldwide gold standard benchmark for excellence in this field.
serves patients from the whole Middle East region, including the Palestinian
Authority and runs a collaboration with Palestinian doctors. The purpose of the
center is to better diagnose, treat and cure patients suffering from primary
immunodeficiency and to characterize and understand the immune system both healthy
and diseased, Somech said.
Article by Judy Siegel-Itzkovich
June 5, 2013