Thalassemias: An Overview

Abstract

Thalassemia syndromes are among the most serious and common genetic conditions. They are indigenous in a wide but specific geographical area. However, through migration they are spreading across regions not previously affected. Thalassemias are caused by mutations in the α (HBA1/HBA2) and β globin (HBB) genes and are usually inherited in an autosomal recessive manner. The corresponding proteins form the adult hemoglobin molecule (HbA) which is a heterotetramer of two α and two β globin chains. Thalassemia-causing mutations lead to an imbalanced globin chain production and consecutively to impaired erythropoiesis. The severity of the disease is largely determined by the degree of chain imbalance. In the worst case, survival is dependent on regular blood transfusions, which in turn cause transfusional iron overload and secondary multi-organ damage due to iron toxicity. A vigorous monitoring and treatment regime is required, even for the milder syndromes. Thalassemias are a major public health issue in many populations which many health authorities fail to address. Even though comprehensive care has resulted in long-term survival and good quality of life, poor access to essential components of management results in complications which increase the cost of treatment and lead to poor outcomes. These requirements are not recognized by measures such as the Global Burden of Disease project, which ranks thalassemia very low in terms of disability-adjusted life years (DALYs), and fails to consider that it ranks highly in the one to four-year-old age group, making it an important contributor to under-5 mortality. Thalassemia does not fulfil the criteria to be accepted as a target disease for neonatal screening. Nevertheless, depending on the screening methodology, severe cases of thalassemia will be detected in most neonatal screening programs for sickle cell disease. This is very valuable because: (1) it helps to prepare the affected families for having a sick child and (2) it is an important measure of secondary prevention.

Adaptation to Mediterranea

“…The onset of symptoms will appear 12 months after the birth, [67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85], at the moment when HbF production switches to adult and physiological synthesis of HbA is yet to be established [86]. The infants will experience feeding problems, recurrent fevers, diarrhea, enlargement of the abdomen and the growth retardation.…”

The Rare Anaemias

“…While point mutations predominate in beta genes, large deletions are more frequent in alpha genes. According to the type of mutation and the intensity of the synthesis decrease, the severity of the clinical picture can be more or less intense [23]. In beta thalassemia the milder forms consist of a slight or moderate hypochromic and microcytic anaemia (thalassemia trait) whereas the more severe clinical forms can be classified as "thalassemia major" or "thalassemia intermedia" depending on the severity of the anaemia and the periodic transfusion requirements, respectively.…”

Beta Thalassemia Major: Overview of Molecular Etiology, Pathophysiology, Current and Novel Therapeutic Approaches

“…Haemoglobin is a tetramer, made up of 4 identical protomers 2 to 2. Each protomer is composed of a globin (alpha or beta chain of globular glycoproteins) and heme which carrying an iron atom [8].…”

“…In bêta-thalassemia, this equilibrium is perturbed by the defective production of bêta globin chains resulting from mutations in the beta-globin gene leading to accumulation of globin chains and causing anemia and an increase in HbF and HbA2 as The physiological situation is characterized by a balanced production of theα and the that ensures a pairing into the normal tetramers. In thalassemia, this equilibrium is perturbed by the defective production of bêta om mutations in the ne leading to accumulation of α causing anemia and an increase in HbF and HbA2 as there are decreased beta chains for HbA formation [8].…”