This disease is caused from the homozygous genetic condition for a severe β thalassaemic defect (in Italy very often the mutation β039, C→T) or from the compound heterozygosis for 2 severe β thalassaemic defects.
The Mediterranean anaemia (or thalassemia major or Cooley's anaemia) manifests in the first months of the child life: with severe pallor, reduced appetite, failure to thrive and recurrent feverish episodes. There are manifestations of a serious anaemia. The red blood cells are very few and almost entirely deprived of hemoglobin; have enormous and different forms, many are only fragments of erythrocytes (schistocytes), and, because of these serious alterations, all go toward a precocious destruction.
Already since the first months of life, the child requires blood transfusions otherwise he does not survive. In fact, in absence of transfusions, if he succeeds in surviving for a few years, he manifests progressive, serious skull-facial characters, mongoloid physiognomy and "hair on end" appearance on plain skull radiographs: all consequences of the enormous expansion of the bone marrow that however produce only unviable erythrocytes (ineffective erythropoiesis). Meanwhile haepato-splenomegaly, growth retardation, absence of puberal development and heart failure appear. These conditions are a common cause of death in affected persons.
Mediterranean anaemia Therapy
After receiving regular and all the life blood trasfusions, child lives, grows and is well.
After one year, from the beginning of this therapy, however he has to begin the care with a drug that succeeds in making to eliminate at least a part of the iron received with the haemotransfusions (iron chelation therapy). Since almost thirthy years, this therapy is practised administering a drug, the desferrioxamine, with a slow subcutaneous infusion using a disposable infuser (for over 6h) 6 times per week. Since few years, the deferiprone, a drug with oral administration, is also used, that however has not totally replaced the desferrioxamine use.
During the life, the patient also needs a lot of other therapies: in the adolescence, hormonal therapies in order to undergo a sufficient puberal development; later the cares, to slow down the cardiopathy e haepatopathy course and to fight the infection in patients who have contracted HCV often as consequence of the haemotransfusional therapy. In the adolescence, usually the splenectomy is also necessary.
With all these cares, the child succeeds in regularly growing, preserve a normal aspect, becomes a teen-ager and then a youth that can develop both a normal working activity and can also get married.
Bone marrow transplantation: a definitive care of the Mediterranean anaemia
Currently, the bone marrow transplantation is the only therapy that allows a definitive recovery.
Since more than twenty years, it is performed in Mediterranean anaemia patients. The marrow must be collected by a HLA-matched identical and healthy, possibly not thalassaemic, sibling donor (generally brother or sister) has been successfully used for a sick child transplantation.
If patients are still in childish age and have received few transfusions, do not have a serious haepatic and myocardiac siderosis and have not contracted haepatitis, the recovery is gotten in 100% of the cases.
Since the beginning of the 1990s the transplantation methodology has recorded new important changements. The in toto bone marrow employment is replaced by using only the stem cells, strongly immature cells that can indefinitely renew themselves and can mature growing into a high number of erythocytes. Potential stem cell sources can be: the bone marrow of healthy subjects or the foetal liver, or the easily available umbilical cord blood. In some case, these cells can even be transplanted in foetus, by the umbilical cord blood of a healthy brother, directly in utero. This experimentation is still in progress but has not given results to be able to overcome the phase of studies carried out till now.
Gene Therapy: the future of the Mediterranean anaemia
Also, a practical application of the gene therapy, that could allow reaching a definitive recovery of the bone marrow, remains to be demonstrated. This therapy provides the insertion, in the genetic patrimony of the patient, of a β normal globin gene in place of the absent or close to the mutated one. Studies are still in progress and by now only relate to the use of laboratory animals.
