Hemoglobin Disease: Sickle Cell - Block 2

The given statement is true. Variants are forms of a gene that contain a change, which can either be benign or cause disease. In most cases, variants lead to a single amino acid substitution due to a point mutation. This means that there is a change in the genetic code at a specific location, resulting in a different amino acid being incorporated into the protein.

Hb structure: Sickle cell disease
Hb synthesis: Thalassemias

Hemoglobin is a protein found in red blood cells that is responsible for carrying oxygen throughout the body. After birth, hemoglobin is indeed produced in the bone marrow. The bone marrow is a soft, spongy tissue found inside bones, and it is responsible for producing red blood cells, including hemoglobin. Therefore, the statement is true.

Hemoglobin A (HbA): Adult, by 3months of age almost all the Hb is adult type

The correct answer is "ischemia and infarctions". In sickle cell disease, the abnormal sickle-shaped red blood cells can block the small blood vessels, leading to decreased blood flow and oxygen supply to the tissues. This can result in tissue damage and ischemia (lack of blood flow) in various organs. Additionally, the blockage of blood vessels can also cause infarctions (tissue death) in the affected areas.

A Hemoglobin (Hb) molecule consists of four polypeptide chains, 2 alpha and 2 Beta chains. Each Hb subunit contains a single heme moiety, which is a protoporphyrin complexed with a single iron atom. Each heme can bind one oxygen molecule, and since there are four heme groups in a hemoglobin molecule, it can transport a total of four oxygen molecules.

Sickle HbSC is usually milder in severity of the disease compared to HbSS.
Sickle B+ Thalassemia: the sickle cell allele inherited from one parent and the B allele from other parent.
Sickle B* Thalassemia: No production of Beta

HBC is Glu to Lys on bet chain 6
HbF is Glu to Lys on beta chain residue 26
These changes lead to clinical manifestations

and via molecular biology: PCR analysis

B* Thalassemia is a genetic disorder that affects the production of hemoglobin, the protein responsible for carrying oxygen in the blood. In this condition, there is a mutation in the beta globin gene, leading to a decrease or absence of beta globin expression. As a result, the production of normal hemoglobin is impaired, causing anemia and other complications. Therefore, the statement that B* Thalassemia has no beta globin expression is true.

After birth, there is a decrease in the expression of the gamma globin gene and a simultaneous increase in the expression of the beta globin gene. This change in expression is known as the "globin switch." It refers to the transition from the production of fetal hemoglobin (gamma globin) to adult hemoglobin (beta globin). This switch is essential for the proper functioning of red blood cells and is a normal developmental process that occurs after birth.

Infections are a major cause of death at all ages with sickle cell. This is because individuals with sickle cell disease have a weakened immune system, making them more susceptible to infections. Infections can lead to complications such as pneumonia, meningitis, and sepsis, which can be life-threatening for individuals with sickle cell. Prompt and appropriate treatment of infections is crucial in managing sickle cell disease and reducing the risk of mortality.

During the 5th week of gestation, hematopoiesis, which is the formation of blood cells, occurs in the fetal yolk sac. This structure plays a crucial role in the early development of the embryo, providing nutrients and supporting the growth of the fetus. As the pregnancy progresses, hematopoiesis gradually shifts to other organs such as the liver and spleen, and eventually settles in the bone marrow. However, during the 5th week, the fetal yolk sac is primarily responsible for producing blood cells.

During fetal development, the liver and spleen are responsible for producing hemoglobin. These organs play a crucial role in the production of red blood cells, including hemoglobin, which is responsible for carrying oxygen throughout the body. As the fetus grows and develops, the liver and spleen gradually decrease their role in hemoglobin production, and the responsibility is taken over by the bone marrow after birth.

Repeated sickling and unsickling produce irreversible sickled cells that are removed by the spleen. The rate of removal exceeds the production leading to anemia.