1. The Unstable Haemoglobins
A range of VERY rare conditions
All easily mistaken for thalassaemia major

2. A brief recap – beta thalassaemia
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
well compensated
Hb A2 a2d2

3. A brief recap – beta thalassaemia
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

4. Meanwhile in Indianapolois
A nine year old girl with:
fatigue
anaemia with reticulocytosis
bone marrow hyperplasia & hypersplenism
a father with exactly the same
Looks clinically like thalassaemia major, but…..
no known beta thalassaemia gene mutation was detected

5. Meanwhile in Indianapolois
Hb Indianapolis
b112 cys --> arg
Very unstable b chain
Very unstable haemoglobin
haemoglobin precipitates just like in thalassaemia

6. And other unstable Hbs…..
Other Substituions
Hb Indianapolis
β 112 cys → arg
Hb Bushwick
β 74 gly → val
Hb Morgantown
β 91 ctg → cg
Hb Showa-Yakushiji
β110 leu → pro
Hb Shanghai
β 131 gln → pro

7. And other unstable Hbs…..
Shortened globin
Hb Sainte Seve
β 127 gln → Stop !

8. And other unstable Hbs…..
Frame Shifts
Hb Stara Zagora
β 137 – bp
Hb Nijkerk
β bp

9. And other unstable Hbs…..
Alpha Chain
Hb Evanston
a 14 trp → arg
Hb Questembert
a 131 ser → pro
Hb Kansas City
a 46 phe → ser
Hb Zurich Albisrieden
a 59 gly → arg
a 35 ser → pro a

10. And other unstable Hbs…..
Fusion Globin
Hb Lepore Xanthi
d17 / β 22 fusion

11. To summarise Clinical Problem in thalassaemia:
Functional lack of a or b globin chains in haemoglobin
Various reasons
Exactly the same problem with an unstable haemoglobin