Haemoglobin Flashcards

Question

What are the two types of thalassemias?

Answer 1

α-Thalassaemia – disruption to α-globin β-Thalassaemia – disruption to β-globin

Answer 2

Deletional α-Thalassaemia - result of α-globin locus deletions of varying size Non-Deletional α-Thalassaemia - due to mutation(s) in either the α2 or the α1 globin genes resulting in an imbalance of the α:β globin ratio

Answer 3

Cause of 95% of α-globin aberrations (95%) Due to deletions of either portions of the α-globin genes themselves or the gene regulatory elements that control their expression Deletions are often difficult to detect using simpler DNA technologies as there are usually two copies of the genes

Answer 4

Multiplex Ligation-dependant Probe Amplification (MLPA) Multiplex GAP-PCR protocol (detection of deletions)

Answer 5

Less common form of α-Thalassaemia Due to mutations in either the α2 or α1 globin genes resulting in an imbalance of the α:β globin ratio.

Answer 6

Initiation codon mutations Frameshift mutations Mutations affecting RNA splicing Exonic mutations Nonsense mutations

Answer 7

Greatly reduced rate of α-globin synthesis results in anaemia. Excess of β-globin often results in β4 tetramers: β2/β2 Haemoglobin H has high O₂ affinity, meaning it can't come off to get to the tissues that need it. It is also unstable and precipitates, causing damage to the red cell membrane, resulting in haemolysis.

Answer 8

Total failure of α-globin production. Almost all of the haemoglobin present is Hb Barts (γ2/γ2) or HbH (β2/β2) These are unstable and have very high O₂ affinity, resulting in very poor O₂ delivery to the tissues. Most foetuses die in utero. Some may survive to term but the condition is not compatible with extra-uterine life

Answer 9

If the ζ gene is deleted in the homozygous state, the fetus dies in early gestation resulting in miscarriage.

Answer 10

Results from loss or reduced rate of synthesis of one or both of the β-globin genes. Most commonly due to point mutations or small deletions in the β-globin gene locus.

Answer 11

Promoter Initiation Codon Splicing Nonsense mutations Termination codon mutations

Answer 12

β0 – No β-globin expression from the affected gene (patient is Null for β-globin) β+ - Reduced production of β-globin

Answer 13

Affected individual has one normal β-globin gene and one with a mutation. Usually no health problems other than a possible mild anaemia.

Answer 14

Affected individual has 2 abnormal β-globin genes but still producing some globin. May have splenomegaly, bony deformities. The severity of the anaemia depends on the mutations present. This condition may require occasional transfusion.

Answer 15

This is the most severe form of β-Thalassaemia. Patient has two faulty β-globin genes that cause severe or complete lack of β-globin production. Excess ⍺-globin precipitates causing membrane damage to developing erythroid cells. Result is ineffective erythropoiesis and shortened RBC survival leading to severe transfusion dependent anaemia. Usually presents in the first year of life from the age of three months

Answer 16

HbE is one of the most common structural variant with β-thalassaemic phenotype. It’s an abnormal haemoglobin with a single point mutation in the β-globin chain. The HbE mutation affects β-gene expression by creating an alternate splice site in the gene’s mRNA at codons 25-27. This mutation weakens the interaction between α and β globin

Answer 17

Sickle-cell anaemia or haemoglobin S results from a point mutation at codon 6GAG>GTG (Glu>Val) in the βglobin chain. Deoxygenated HbS undergoes polymerisation. When the polymer is present in sufficient quantities, it causes “sickling” of the red cell.

Answer 18

Haemolysis Vaso-occlusion

Answer 19

- Painful bone crises - Acute chest syndrome - Stroke - Renal Impairment - Liver disease - Splenic infarction - Retinopathy Obstetric complications

Answer 20

Molecular tests can identify globin gene alterations Deletions – MLPA, GAP-PCR Point mutations – DNA sequencing (& MLPA) Biochemical tests can identify changes to globin proteins Alkaline electrophoresis High-performance liquid chromatography (HPLC)

Haemoglobin Flashcards

(44 cards)