haemoglobinopathies and thalassaemia Flashcards
Describe the relationship between haemoglobinopath and thalassaemias.
Haemoglobinopathies involve molecular defects in the haemoglobin protein, while thalassaemias result from defects in the synthesis of globin chains.
What is the difference between a haemoglobinopathy and thalassaemia in terms of defect type?
Haemoglobinopathy is a qualitative defect due to a mutation in the coding sequence of a globin gene, while thalassaemia is a quantitative defect caused by a mutation in the non-coding sequence of a globin gene.
How do haemoglobinopathies and thalassaemias overlap?
Some thalassaemias can also be haemoglobinopathies, as conditions affecting globin proteins may also impact their production.
Define sickle cell disease.
Sickle cell disease is a condition where a mutation in a single amino acid leads to the clinical symptoms of sickle cell anaemia.
What is the consequence of a Glu to Val mutation in haemoglobin?
The mutation causes self-association and polymerization of haemoglobin tetramers.
How does the Glu to Val mutation in haemoglobin lead to polymerization?
The Val-6 on one subunit binds to a hydrophobic patch on another subunit, initiating a chain reaction of binding between subunits.
Describe the polymerization process of haemoglobin S in sickle cell disease.
The Glu to Val mutation causes subunits to bind to each other, forming long chains of hemoglobin tetramers, leading to polymerization.
What facilitates the polymerization of hemoglobin S in sickle cell disease?
The process is facilitated by the very high concentration of hemoglobin in erythrocytes.
How does the crystal structure of sickle-cell deoxyhemoglobin contribute to understanding the disease?
It reveals the arrangement of subunits and the binding pattern that leads to polymerization, providing insights into the molecular basis of sickle cell disease.
Describe the polymerization process of hemoglobin S.
Polymerization of hemoglobin S involves the binding of Val-6 on one β-subunit to the “hydrophobic patch” on another β-subunit in a different tetramer, leading to the formation of strands with a regular, symmetrical helical structure.
What is the effect of hemoglobin fibers on the shape of erythrocytes in sickle cell disease?
Growing fibers of HbS distort the shape of erythrocytes from a bi-concave disc to an irregular shape, ultimately resulting in the characteristic sickle cell shape.
Define sickle cell crisis in sickle cell disease.
Sickle cell crisis refers to episodes where symptoms of sickle cell disease are exacerbated, leading to acute pain and other complications.
How do genetics play a role in sickle cell disease?
Genetics contribute to sickle cell disease by causing the abnormal hemoglobin S to polymerize under certain conditions, leading to the characteristic symptoms of the disease.
Describe the therapies used for sickle cell disease.
Therapies for sickle cell disease include transfusion, attempts to induce expression of fetal hemoglobin (HbF), and the use of hydroxyurea to reduce erythrocyte sickling.
What are the risk factors that can trigger sickle cell crisis?
Risk factors for sickle cell crisis include exercise, altitude, cold, dehydration, alcohol consumption, pregnancy, and infection.
How do hemoglobin fibers contribute to the symptoms of sickle cell disease?
Hemoglobin fibers lead to the distortion of erythrocyte shape, increased fragility, and clumping of cells, causing blockages in microcirculation and various symptoms of sickle cell disease.
Describe the structure of hemoglobin fibers formed in sickle cell disease.
Hemoglobin fibers in sickle cell disease consist of regular 14-strand helical structures formed by the alignment of strands, resulting from the polymerization of hemoglobin S.
What is the role of fetal hemoglobin (HbF) in the treatment of sickle cell disease?
Fetal hemoglobin (HbF) is used in therapies for sickle cell disease to reduce erythrocyte sickling, as it does not participate in the polymerization process like hemoglobin S.
