THALASSEMIAS AND HEMOGLOBINOPATHIES OVERVIEW

Introduction

Thalassemias and hemoglobinopathies are two different types of genetic blood disorders that affect the production of hemoglobin, the protein in red blood cells that carries oxygen throughout the body.

Thalassemias are a group of inherited blood disorders that affect the production of one or more of the globin chains that make up hemoglobin. There are two main types of thalassemia: alpha thalassemia and beta thalassemia. Alpha thalassemia occurs when there is a deficiency in the production of alpha globin chains, while beta thalassemia occurs when there is a deficiency in the production of beta globin chains. The severity of thalassemia varies depending on the number of affected globin chains and can range from mild to life-threatening.

Hemoglobinopathies are a group of inherited blood disorders that result from mutations in the genes that control the production of hemoglobin. The most common hemoglobinopathies are sickle cell anemia and hemoglobin C disease. Sickle cell anemia is caused by a mutation in the beta globin gene that leads to the production of abnormal hemoglobin molecules that can cause red blood cells to become stiff and take on a sickle shape, which can block blood vessels and cause severe pain and other complications. Hemoglobin C disease is caused by a mutation in the beta globin gene that leads to the production of abnormal hemoglobin molecules that can cause red blood cells to become stiff and take on a round shape, which can cause mild to moderate anemia and other complications.

Both thalassemias and hemoglobinopathies are inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder. These conditions are most commonly found in people of Mediterranean, African, Middle Eastern, and Southeast Asian descent. Treatment options for thalassemias and hemoglobinopathies vary depending on the severity of the condition and may include blood transfusions, bone marrow transplants, and medications to manage symptoms and complications.

 

In normal blood, there are several types of hemoglobin (Hb) that are present. The most common types of hemoglobin found in adults are:

1) HbA (Alpha-globin and Beta-globin chains) – This is the most common type of hemoglobin found in adults, accounting for approximately 97-98% of all hemoglobin in the body.

2) HbA2 (Alpha-globin and Delta-globin chains) – This type of hemoglobin makes up approximately 1-3% of all hemoglobin in the body.

3) HbF (Fetal hemoglobin, Alpha-globin and Gamma-globin chains) – This type of hemoglobin is found in fetuses and newborns and gradually decreases over the first year of life. In adults, it makes up less than 1% of all hemoglobin.

4) HbS (Sickle cell hemoglobin, Alpha-globin and Beta-globin chains with a mutation in the beta-globin gene) – This type of hemoglobin is not present in normal blood. It is produced in people with sickle cell disease, where the mutation causes the hemoglobin to form into a sickle shape, leading to various health problems.

The percentage of each type of hemoglobin can vary slightly depending on factors such as age, gender, and health status. The values given above are generally representative of healthy adults.

 

Thalassemia syndromes are a group of inherited blood disorders that affect the production of hemoglobin in red blood cells. There are two main types of thalassemia: alpha and beta thalassemia.

1) Basic genetic defect: The basic genetic defect in thalassemia is a mutation in one or more of the genes that control the production of hemoglobin. In alpha thalassemia, there are four genes involved in the production of alpha globin chains, and mutations in one or more of these genes can cause alpha thalassemia. In beta thalassemia, there are two genes involved in the production of beta globin chains, and mutations in one or both of these genes can cause beta thalassemia.

 

2) Red cell morphology: The red cell morphology in thalassemia can vary depending on the severity of the disease. In alpha thalassemia, there may be a mild microcytic hypochromic anemia (small, pale red blood cells). In beta thalassemia, the red blood cells may be severely microcytic and hypochromic, with a high red cell distribution width (RDW) indicating anisocytosis (varying cell sizes).

 

3) Clinical manifestations and complications: The clinical manifestations and complications of thalassemia depend on the type and severity of the disease. In alpha thalassemia, the clinical manifestations may range from asymptomatic to severe anemia requiring blood transfusions. In beta thalassemia, the clinical manifestations may include severe anemia, growth retardation, skeletal deformities, splenomegaly, and jaundice. Complications of thalassemia may include iron overload due to frequent blood transfusions, infections, and complications related to the spleen, such as splenic sequestration crises.

 

4) Diagnostic procedures: Diagnosis of thalassemia involves a combination of clinical evaluation, laboratory tests, and genetic testing. Laboratory tests may include a complete blood count (CBC), hemoglobin electrophoresis, and iron studies. Genetic testing can confirm the diagnosis and determine the specific mutation involved. Prenatal testing can also be done to diagnose thalassemia in a fetus if there is a family history of the disease.

 

1) Basic genetic defect: Sickle cell disease is caused by a mutation in the HBB gene, which provides instructions to make beta-globin, a protein that is part of hemoglobin. The mutation causes a change in the amino acid sequence of beta-globin, resulting in the production of abnormal hemoglobin called hemoglobin S. Individuals with sickle cell trait have one copy of the mutated gene and one normal gene, while those with sickle cell disease have two copies of the mutated gene.

 

2) Red cell morphology: The abnormal hemoglobin in sickle cell disease causes the red blood cells to become sickle-shaped instead of the normal biconcave disc shape. The sickle-shaped cells are less flexible and can block small blood vessels, leading to reduced blood flow and oxygen supply to tissues and organs.

 

3) Clinical manifestations and complications: Sickle cell disease can cause a wide range of clinical manifestations and complications, including pain crises, chronic anemia, increased susceptibility to infections, delayed growth and development, stroke, organ damage (especially the spleen, lungs, and kidneys), and increased risk of certain cancers. Individuals with sickle cell trait generally do not have symptoms, but they may be at increased risk of certain complications, such as exercise-related rhabdomyolysis, heat illness, and splenic infarction.

 

4) Diagnostic procedures: Sickle cell disease and trait can be diagnosed through a variety of methods, including newborn screening, hemoglobin electrophoresis, DNA analysis, and family history evaluation. Newborn screening programs typically use a combination of blood tests to identify infants with sickle cell disease or trait. Hemoglobin electrophoresis separates the different types of hemoglobin in the blood and can identify the presence of abnormal hemoglobin such as hemoglobin S. DNA analysis can confirm the presence of the HBB gene mutation. Family history evaluation can identify individuals who may be carriers of the sickle cell trait and at risk of having a child with sickle cell disease.