1. A range of disorders arising from imbalanced globin production
The Thalassaemias
A range of disorders arising from imbalanced globin production

2. The Thalassaemias To recap And these chains are all “normal”
Haemoglobin A has two a and two b chains (>95% of total Hb)
Haemoglobin A2 has two a and two d chains (2-3% of total Hb)
Haemoglobin F has two a and two g chains (<1% of total Hb)
And these chains are all “normal”

3. The Thalassaemias and you’ve got one beta globin gene on chromosome 11
each cell has two chromosomes 11
a total of two beta globin genes exist in each cell.
two alpha globin genes on chromosome 16
each cell has two chromosomes 16
a total of four alpha globin genes exist in each cell.

4. The Beta Thalassaemias
Major
Two malfunctioning/absent genes
No production of beta chains
surplus production of alpha chains
which precipitate on cell membranes
haemolysis & inefficient haemopoesis
haemopoetic hyperplasia
Minor
One malfunctioning/absent gene
reduced production of beta chains
surplus production of alpha chains
which is compensated well by the body
Hb A2 a2d2

5. The Beta Thalassaemias
Intermedia
Midway in severity between minor and major
reduced production of beta chains
surplus production of alpha chains
which is compensated well by the body
One or two malfunctioning genes ?!?!?!?!
Hb A2 a2d2

6. The Beta Thalassaemias
Population
β-gene Mutation
Severity
Indian
-619 del βο
Mediterranean
-101
β++
African
-88
Mediterranean; African
-87
Japanese
-31
-29
Southeast Asian
-28
Mediterranean; Asian Indian
IVS1-nt1
IVS1-nt5 Βο
ΙΩΣ1-nt6
β+/++
IVS1-nt110 β+
Chinese
IVS2-nt654
IVS2-nt745
codon 39
codon 5
Mediterranean; African-American
codon 6
codons 41/42
African-American
AATAAA to AACAAA

7. The Beta Thalassaemias
Normal beta genes
Either absent
or on a “go-slow”
Hb Barts g4
Raised Hb A2

8. The Alpha Thalassaemias
To recap
Haemoglobin A has two a and two b chains (>95% of total Hb)
Haemoglobin A2 has two a and two d chains (2-3% of total Hb)
Haemoglobin F has two a and two g chains (<1% of total Hb)
And these chains are all “normal”
two alpha globin genes on chromosome 16
each cell has two chromosomes 16
a total of four alpha globin genes exist in each cell.

9. Hydrops fetalis (major)
The Alpha Thalassaemias
a globin problems are often clinically silent
one “duff” gene has three backups
Genotype
α Genes
Description
αα/αα 4
Normal
αα/α- 3
Silent carrier
--/αα or α-/α- 2
Thal minor/trait
--/α- 1
Hgb H disease
--/--
Hydrops fetalis (major)

10. The Alpha Thalassaemias
In the absence of a chains, the b and g chains can form tetramers
Hb H b4
Hb Barts g4