Thalassemia is known to be an inherited genetic blood disorder that results in mild to severe anemia due to the abnormal formation of hemoglobin. Thalassemia is inherited by either one or both parents. A mutation in either chromosome 11 (Deisserot et al, 1978) effect the synthesis of beta hemoglobin, whereas a mutation on chromosome 16 affect the synthesis of alpha hemoglobin(Deisserot et al, 1977). Hemoglobin is a tetramer made of two alpha chains and two beta chains (Cao et al, 2010). The location of the mutation in the hemoglobin chains is what characterizes the severity and type of thalassemia. Geographically thalassemia is commonly found in places like south-east asia and china (Charoenphandhu et al, 2011).
There are two types of thalassemia, …show more content…
Iron overload is due to the chronic transfusions needed to regulate effective red blood cells. The regulation and metabolism of iron is dependant on the regulatory hormone that is produced in the liver, known as hepcidin. Hepcidin helps regulate body iron homeostasis by determining the magnitude of dietary iron release from the enterocytes and stored iron release from reticuloendothelial macrophages (Feng, 2012). When activated it regulates the degradation of Ferroportin which is responsible for the transport of iron throughout the body. Normally hepcidin concentrations will increase in the presence of inflammation and iron overload (Silvestri et al, 2008). However low levels of hepcidin are found in thalassemic patients which causes iron deposition in major organs of the body. In turn this will lead to organ failure and eventually death (Gardenshi et al, 2007). The activation of SMAD 1,5,8/SMAD 4 complex is what causes the expression of hepcidin. Osteoporosis is a result of a decrease in low bone density and is frequently found in thalassemic patients and rodents (Charoenphandhu et al, 2011). In fact 33% to 20% of thalassemic patients experience osteopenia, a less severe form of osteoporosis, and are at a higher risk for bone fracturing. Low bone mass density is experienced in about 90% of transfusion dependant transfusion thalassemic patients (Gurevitch et …show more content…
Iron overload is lethal, yet the mechanism as to how was poorly understood. A study in 1987 by Van Wyck studied the homeostasis of iron in beta thalassemic mice. The ratio of alpha and beta globin genes should be equal in order to produce effective hemoglobin. Thalassemic mice however do not have this ratio; the mutation causes an imbalance. Heterozygous mutation in mice, which is a single defective gene in one allele, hemoglobin can still assemble with at least one beta globin gene, alpha and beta synthesis can still be completed at least at a basal level. However in homozygous mutations, they contain a mutation in both alleles resulting in an incomplete set of alleles thus the synthesis of alpha and beta chains are
There are two types of thalassemia, …show more content…
Iron overload is due to the chronic transfusions needed to regulate effective red blood cells. The regulation and metabolism of iron is dependant on the regulatory hormone that is produced in the liver, known as hepcidin. Hepcidin helps regulate body iron homeostasis by determining the magnitude of dietary iron release from the enterocytes and stored iron release from reticuloendothelial macrophages (Feng, 2012). When activated it regulates the degradation of Ferroportin which is responsible for the transport of iron throughout the body. Normally hepcidin concentrations will increase in the presence of inflammation and iron overload (Silvestri et al, 2008). However low levels of hepcidin are found in thalassemic patients which causes iron deposition in major organs of the body. In turn this will lead to organ failure and eventually death (Gardenshi et al, 2007). The activation of SMAD 1,5,8/SMAD 4 complex is what causes the expression of hepcidin. Osteoporosis is a result of a decrease in low bone density and is frequently found in thalassemic patients and rodents (Charoenphandhu et al, 2011). In fact 33% to 20% of thalassemic patients experience osteopenia, a less severe form of osteoporosis, and are at a higher risk for bone fracturing. Low bone mass density is experienced in about 90% of transfusion dependant transfusion thalassemic patients (Gurevitch et …show more content…
Iron overload is lethal, yet the mechanism as to how was poorly understood. A study in 1987 by Van Wyck studied the homeostasis of iron in beta thalassemic mice. The ratio of alpha and beta globin genes should be equal in order to produce effective hemoglobin. Thalassemic mice however do not have this ratio; the mutation causes an imbalance. Heterozygous mutation in mice, which is a single defective gene in one allele, hemoglobin can still assemble with at least one beta globin gene, alpha and beta synthesis can still be completed at least at a basal level. However in homozygous mutations, they contain a mutation in both alleles resulting in an incomplete set of alleles thus the synthesis of alpha and beta chains are