Introduction to Beta Thalassemia

**3**

**Chapter 1**

Introductory Chapter:

*Marwa Zakaria and Tamer Hassan*

**1. What we need to know about β-thalassemia**

reabsorption secondary to ineffective erythropoiesis.

**1.1 β-Thalassemia: types and clinical presentation**

Thalassemia is a hereditary, autosomal recessive blood disorder due to partial or complete deficiency in the synthesis of or β-globin chains (β-thalassemia) or α-globin chains (α-thalassemia) that compose the major adult hemoglobin resulting

β-Thalassemia is caused by mutations in the HBB gene resulting in decrease of the production of β chain leading to excessive accumulation of unpaired α chains that aggregate and precipitates along the red cell membranes, causing their damage and resulting in intravascular hemolysis. Also, premature destruction of erythroid precursors results in intramedullary death and ineffective erythropoiesis and a short lifespan of mature RBCs in the circulation. Frequent RBC transfusion is the main supportive therapy, leading to excessive accumulation of iron (iron overload), a condition that is exacerbated by excessive hemolysis and the increased iron

Excessive iron is toxic and catalyzes the generation of reactive oxygen species, which in excess are toxic, causing damage to numerous body organs such as the heart and liver as well as the endocrine system. Herein, we represent an overview on thalassemia regarding the underlying pathophysiology of the disease, clinical presentations, and potential therapeutic modalities for the amelioration of its complications, as well as new modalities that may provide a cure for the disease. Thanks to the significant improvement in therapy, patients with β-thalassemia may

In the homozygous state of β-thalassemia which is known as thalassemia major represented with severe, transfusion-dependent anemia within the first 2 years of life. Also associated with skeletal abnormalities and poor growth, in the heterozygous state of β-thalassemia (trait or minor) causes mild to moderate microcytic anemia and not require any specific management. On the other hand, patients in whom clinical severity of the disease lies between that of thalassemia major and thalassemia trait are classified as having β-thalassemia intermedia and require only periodic blood transfusions under special circumstances [1]. Numerous different genotypes are associated with β-thalassemia intermedia, such as HbE which is a common Hb variant found in Southeast Asia, and this variant is included in the beta thalassemia category of diseases. Also, HbS (sickle cell disease) can be presented

Repeated blood transfusions resulting in excessive iron deposition and generation of ROS is a leading cause of morbidity and mortality, in those patients [3].

β-Thalassemia

in chronic hemolytic state.

reach an advanced age.

clinically with severe anemia [2].

#### **Chapter 1**
