Beta Thalassemia Flashcards
How is thalassemia inherited? What is the chance that heterozygous parents will have a child with thalassemia or carrier?
Thalassemia is typically inherited as an autosomal recessive trait, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder.
If both parents are carriers (heterozygous) of the thalassemia gene, there is a 25% chance with each pregnancy that their child will inherit thalassemia, a 50% chance of being a carrier like the parents, and a 25% chance of not inheriting the gene.
What are qualitative hemoglobinopathies?
Qualitative hemoglobinopathies are a type of hemoglobin disorder that result from mutations in the α- or β-globin genes, leading to structural alterations in the hemoglobin molecule. These structural changes can affect the oxygen-carrying capacity and stability of hemoglobin, resulting in various types of abnormal hemoglobin.
What are quantitative hemoglobinopathies?
Quantitative hemoglobinopathies, also known as thalassemias, arise from mutations that cause decreased synthesis of either the α- or β-globin chains, leading to an imbalance of the subunits. In β-thalassemia, there is defective synthesis of the β chain, while in α-thalassemia, there is defective synthesis of the α chain. In some cases, both the δ and β chains may be reduced in a condition called δ-β thalassemia.
What are the normal hemoglobins found in adults?
- HbA (hemoglobin A): α2β2, which accounts for approximately 95% of the total adult hemoglobin.
- HbF (hemoglobin F): α2γ2, which comprises less than 1% of the total adult hemoglobin and is present at high concentrations during fetal life but decreases rapidly after birth.
- HbA2 (hemoglobin A2): α2δ2, which constitutes less than 3.1% of the total adult hemoglobin.
Where are the globin chain structural genes located?
The globin chain structural genes are located on chromosomes 16 and 11. There are two copies of the hemoglobin alpha gene on each chromosome 16 (four α genes per cell), and one β gene on each chromosome 11 (two β genes per cell).
How do gene mutations or deletions cause both α-thalassemia and ß thalassemia?
Deletions of α genes tend to underlie most cases of α-thalassemia. The severity of symptoms depends on how many of these genes are lost. Loss of one or two genes is usually asymptomatic, whereas deletion of all four genes is fatal to the unborn child.
In contrast, over 100 types of mutations affect the ß genes, and deletion mutations are rare. Some mutations tend to cause a reduction, rather than a complete absence, of β- globin chains and so result in milder disease. Other mutations tend to cause total absence of β-globin chains leading to severe disease.
