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Excessive iron absorption is one of the main features of β-thalassemia and can lead to severe morbidity and mortality. Serial analyses of β-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with β-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in β-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in β-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with β-thalassemia and related disorders., Introduction β-thalassemia is one of the most common congenital anemias arising from partial or complete lack of β-globin synthesis. β-thalassemia major, also known as Cooley anemia, is the most severe [...]

A detailed report is presented on thalassemia, an inherited anemia caused by defective hemoglobin production that is the most common global genetic disease. Emphasis is given on improved treatment and prevention of thalassemia in less developed countries, where the disease is more pronounced, through improved education and greater access to prenatal investigation.

Red blood cells (RBCs) in beta-thalassemia show enhanced aggregability and form large clusters as opposed to normal rouleaux. The size of the clusters may reach and even exceed the width of the small blood vessels and thus interfere with blood flow and microcirculation. The RBC aggregates require a greater shear stress to be dispersed. Blood transfusions in thalassemic patients decrease the aggregability of the RBCs. This suggests that the improvement of RBC rheological function may be useful in treating the disorder.

The mutations in the beta-globin poly(A) signals in patients suffering from beta-thalassemia were identified and characterized. The mutations were identified as either point mutations or deletions. Point mutations in the poly(A) tail resulted in expression of 12-34% of normal beta-globin mRNA. The deletions did not produce any normal transcripts, although the patient homozygous for this mutation had a beta/alpha chain ratio of 0.10. These results suggest that the poly(A) signal is not an absolute requirement for mRNA cleavage and the extended RNA is translated in vivo. Further analysis indicates that the primary beta-globin transcriptional unit is > 5 kb long.

Homozygous beta-thalassemia major is a disease affecting infants. The disease causes anemia, lack of oxygen in the blood (hypoxia) and enlargement of the spleen (hypersplenism). Patients require frequent blood transfusions to maintain oxygen levels in the blood. Red blood cells are rapidly destroyed, leaving behind iron deposits in the skin and organs such as the heart, liver and pancreas, causing those organs to fail. Pregnancy involves changes in the force and flow of blood circulation (hemodynamic changes) which may aggravate the damage to organs in a pregnant mother suffering from the disease. Maintaining hemoglobin levels and closely monitoring both mother and fetus may prevent damage to the mother's organs. A case involving a pregnant woman with the disease who delivered a healthy baby is described.

The case of a man who developed tumor lysis syndrome after being treated with an anti-cancer drug is discussed. Tumor lysis syndrome is a severe reaction to chemotherapy and is characterized by abnormal levels of certain metabolites. The 57-year-old patient had chronic lymphocytic leukemia and had been treated previously with several drug regimens. One week after he was treated with 2-chlorodeoxyadenosine, he was admitted to the hospital with fever. Over the next few days, his blood contained increased levels of lactate dehydrogenase, uric acid, creatinine, phosphorus and potassium, and decreased levels of calcium. His white blood cell count decreased, his kidneys failed and he died of a bacterial infection. This patient may have retained toxic levels of 2-chlorodeoxyadenosine due to delayed tumor cell destruction and subsequent kidney failure.