What are Thalassemias?
Thalassemia is a term that encompasses different diseases with a common symptomatology, anemia. Anemia is caused by a decrease in the production of functional hemoglobin, the oxygen-carrying molecule in the blood, causing a decrease in red blood cells.
Thalassemias can be classified according to the affected chain or the severity of the disease. In terms of the affected chain, the most common are alpha and beta, caused by pathogenic variants in the HBA1/2 or HBB genes, respectively.
Regarding the severity of alpha thalassemia, 4 types can be defined from less to more severe: silent alpha thalassemia, alpha thalassemia minor, hemoglobin H disease (HbH), and hydrops fetalis with Bart’s Hb. In the case of beta-thalassemia, 3 types can be distinguished: minor, intermediate and major.
Milder forms of the disease are usually asymptomatic, while more severe forms require frequent blood transfusions. If untreated, the most severe forms of the disease appear during the first years of life, showing a lack of appetite, with slow growth and enlargement of organs such as the liver and heart. These symptoms often lead to death during infancy. Intermediate forms generally consist in anemia of varying severity, but rarely require blood transfusions.
Alpha and beta thalassemias are inherited diseases that are transmitted in an autosomal recessive manner. Consequently, it is necessary that both parents of an affected person are carriers of the same disease (either alpha or beta), being affected with silent or minor thalassemia, so that the affected person with an intermediate or severe form of the disease inherits two altered copies of the same gene.
The most common form of the disease is silent or minor thalassemia (disease carriers), while most thalassemia patients with clinical symptoms show intermediate forms of the disease (HbH or beta thalassemia intermedia).
How are they diagnosed?
Approximately 100,000 people worldwide are diagnosed with severe forms of thalassemia each year. Diagnosis of thalassemias is usually made by blood tests. In patients with milder symptomatology, the diagnosis is usually made on routine testing in adulthood during an episode of anemia, while more severe cases are diagnosed during the first months of life because of signs and symptoms resulting from severe anemia.
In mild or asymptomatic cases, carriers of the disease can be diagnosed by genetic testing. However, although less common, as there are more genes and regions involved in thalassemia, it is recommended to complement the genetic analysis with hemoglobin electrophoresis to confirm negative results.
Is there a treatment?
Mild forms of the disease (silent or minor thalassemia) usually do not require treatment as they rarely show symptoms of the disease or occasionally have mild anemia. They generally have a healthy life without being affected by their carrier status.
More severe forms of the disease require regular blood transfusions along with antibiotics. Since regular blood transfusions result in iron overload it is also necessary to complement the treatment with iron chelators. In these cases the disease can also be treated by bone marrow transplantation.
How can the risk of affected offspring be reduced?
As these are recessively inherited diseases, they can be prevented in the offspring by testing for the HBA1, HBA2 and HBB genes in both members of the couple with reproductive desire. If both partners are identified as carriers of pathogenic variants in the same gene (HBA1/2 or HBB) it is possible to reduce the risk of severe forms of the disease in the offspring by preimplantation diagnosis (PGT-M), prenatal diagnosis or gamete donation with genetically screened donors identified as non-carriers of the disease.
If one or both members of the couple are not identified as carriers of pathogenic variants in the analyzed genes, the risk of the child being affected by severe forms of the disease is reduced by lowering the possibility of inheriting all the copies of the same gene with alterations that can lead to disease.