DR. RAZ SOMECH 370.
(photo credit: courtesy sheba)
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
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
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
It is estimated that there are dozens of such cases in
the Palestinian Authority; none has yet been found among Israeli
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.
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.”
addition to the inbreeding problem, few Arab women agree to undergo
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.
suitable donors were found in the small Arab tissue type registry at
Hadassah-University Medical Center in Jerusalem’s Ein Kerem, Somech
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,
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.
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.
The center 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.