Today is Thalassemia Day. An inherited genetic disorder that affects the ability of red blood cells to carry oxygen in the blood. Rare, but relatively widespread in our country and throughout the Mediterranean area (in the form defined as Beta-thalassemia, also known as Mediterranean anemia), which in the past, in the most serious forms, did not allow patients to survive beyond the tenth, fifteenth year of age. Fortunately, this is no longer the case today: thanks to transfusions and iron chelating therapies, life expectancy has lengthened considerably, and new therapeutic advances promise to revolutionize the natural history of this disease even more radically in the future. On the day dedicated to these patients, let’s take a closer look at the disease they fight every day, how it is treated and what new things are on the way.
Beta-thalassemia, prenatal diagnosis can prevent over 400 cases a year
by Tiziana Moriconi
The different forms of thalassemia
Hemoglobin is the protein that makes our blood red. It is contained in red blood cells and has the fundamental task of allowing the transport of oxygen. In patients with thalassemia, the correct production of hemoglobin is compromised by a hereditary genetic defect, and this creates tissue oxygenation problems, which depend on the degree of severity of the disease, and which can also be very dangerous.
There are two forms of thalassemia, distinguished by which protein sub-unit of hemoglobin is defective. There beta-thalassemia it is widespread in the Mediterranean regions and depends on the impairment of the genes responsible for the composition of the beta chain of hemoglobin. The symptomatology depends on how many genes are altered: if it is only one, it is called thalassemia minor and rarely produces symptoms; when both genes involved in the production of the beta chain are compromised, we speak of thalassemia instead majora pathology that begins with severe symptoms usually within the first two years, and that requires lifelong therapies.
The second form of the disease is called alpha-thalassemia, and depends on the malfunction of the genes that produce the alpha chain of the protein. It is widespread in the Middle East, African countries and Southeast Asia, and again the severity depends on the number of defective genes. In this case, there are 4 of those necessary for the normal production of hemoglobin: if only one is defective, one is a healthy carrier and does not experience symptoms, with two malfunctioning genes one suffers from thalassemia minorwith three of a severe or intermediate form, while carriers of four altered genes usually do not survive birth due to the very severe symptoms of the disease.
Thalassemia, what are the rights of patients?
by Barbara Orrico
Where is it widespread and the link with malaria
The spread of thalassemia somewhat resembles that of malaria. Being healthy carriers of thalassemia, in fact, offers some protection against this infectious disease, which has probably increased the prevalence of defective genes in the populations of the areas where it was widespread. In Italy the most affected areas are Sicily, Sardinia and the Po delta. Patients affected by severe forms of thalassemia are about 7 thousand, while healthy carriers of beta-thalassemia, people with only one malfunctioning gene who can transmit the disease to their offspring if the other parent is also a healthy carrier, are about 3 million. Alpha-thalassemia, on the other hand, as we said, is more common in Africa, the Middle East and Southeast Asian countries. Some studies suggest that almost 5% of the entire world population may be carriers of one of the defective genes involved in the onset of the disease.
What are the symptoms
For healthy carriers (with only one mutated gene), beta-thalassemia usually has no symptoms and can only be detected by blood tests which reveal mild anemia and red blood cells that are smaller and more numerous than normal, a condition called thalassemia. Thalassemia major, on the other hand, begins in the first years of life, with symptoms related to severe anemia: feeling of weakness (asthenia), pale skin, jaundice, gallstones, enlarged spleen and liver. In the most serious cases, the symptoms can degenerate to the point of creating real bone deformities, especially on the face and skull; thalassemia can also favor an abnormal expansion of the bone marrow, both making the bone mass fragile and greatly increasing the risk of bone fractures.
Beta-thalassemia, new indications for the drug against anemia
by Dario Rubino
How to cure
Patients with intermediate or severe forms of thalassemia require periodic transfusions to ensure survival. Transfusions must be carried out every two or three weeks throughout life, and expose the sick to another danger: hemochromatosis, i.e. the accumulation of excessive quantities of iron in the blood, which in turn must be treated with use of iron chelating drugs, to prevent it from causing damage to the body.
Recently, a new drug was also approved in Italy that offers an additional alternative for patients: luspatercept, the progenitor of the class of erythroid maturation agents, which can be used in people with transfusion-dependent anemia, including patients thalassemia, which increases the production of red blood cells and therefore reduces the need for transfusions.
Beta thalassemia, towards a new gene therapy
by Letizia Gabaglio
Healing Goal
In terms of resolutive therapies, capable of definitively curing thalassemia, very interesting results have recently come from gene therapy, which in the studies carried out has made it possible to cure up to 90% of patients, making them independent of the need for transfusions. This form of therapy is being evaluated by the European Medicines Agency. Another possibility, at a less advanced stage of development, is to genetically modify the marrow stem cells that produce red blood cells, to correct the alterations that cause the onset of thalassemia.
Locatelli: “The revolution of advanced therapies must be made accessible to patients”
by Letizia Gabaglio
A strategy that is used today, however, is the heterologous bone marrow transplant, from a compatible sibling or through a biobank. An alternative that offers excellent healing prospects, but which unfortunately is not always possible for all patients.