Thalassaemia
Thalassemia is a group of inherited hemolytic anemia diseases. Thalassemia is an anemia or pathological condition caused by the deficiency or insufficiency of synthesis of one or more globin chains in hemoglobin due to inherited genetic defects.
- Beta-thalassemia
The molecular pathology of the occurrence of β-thalassemia is quite complex, with more than 100 known mutations in the β-gene, mainly due to point mutations in the gene and, in a few cases, gene deletions. - Alpha-thalassemia
Most alpha thalassemia is due to deletion of the alpha globin gene, and a few are caused by point mutations.
Ultrastructure of the hemoglobin molecule [1].
Based on clinical manifestations, thalassemia is divided into transfusion-dependent thalassemia (TDT), which is a severe form of thalassemia (TM) that depends on long-term regular blood transfusions, and non-transfusion-dependent thalassemia (NTDT), which is a group of thalassemia's that do not require blood transfusions or require transfusions only in special cases such as infections, surgery, pregnancy, and growth retardation.
- TDT
Long-term repeated blood transfusions are the main cause of iron overload in patients with TDT. - NTDT
Patients with NTDT are less anemic and therefore this type of patient does not require or only occasionally requires blood transfusion. Decreased hepcidin levels and increased intestinal iron absorption due to ineffective erythropoiesis, anemia, and hypoxia are the main causes of iron overload in NTDT patients.
A new therapeutic target for thalassemia [2].
Iron Metabolism Disorders in Thalassemia
β-thalassemia is a disease characterized by anemia associated with ineffective erythropoiesis and iron dysregulation leading to iron overload. The peptide hormone hepcidin regulates iron metabolism, and insufficient hepcidin synthesis is responsible for iron overload in microtransfused patients with this disorder.
Iron Overload in Thalassemia
Several studies have shown that hepcidin is chronically suppressed in thalassemia. In the presence of systemic hypoxia, hepcidin expression is reduced to increase iron delivery to expanded erythrocytes. Inappropriately low levels of hepcidin can lead to iron overload, as in intermediate beta-thalassemia and other disorders characterized by ineffective erythropoiesis.
Oxidative Stress in Thalassemia
In thalassemia, increased erythrocyte destruction and excessive intestinal iron absorption result in high iron levels. Over time, hepatocytes become saturated with transferrin-binding capacity as well as iron storage capacity. Subsequently, non-transferrin-bound iron appears in the plasma. This form of iron is extremely reactive and catalyzes the formation of dangerous reactive oxygen species (ROS), which leads to membrane protein oxidation, structural membrane changes, and altered signaling pathways.
The key to the treatment of thalassemia is finding better treatment options and avoiding complications, which requires an in-depth understanding of the underlying biology of the disease at the cellular and molecular levels. Protheragen has many years of research experience in the field of thalassemia research. If you are interested in the services we offer, please contact us for more information.
References
- Shafique F, et al. Thalassemia, a human blood disorder[J]. Brazilian Journal of Biology, 2021, 83.
- Cappellini M D, et al. New therapeutic targets in transfusion-dependent and-independent thalassemia[J]. Hematology 2014, the American Society of Hematology Education Program Book, 2017, 2017(1): 278-283.