A range of VERY rare conditions All easily mistaken for thalassaemia major

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 A2a2d2

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…..

7. And other unstable Hbs…..

8. And other unstable Hbs…..

9. And other unstable Hbs….. a

10. And other unstable Hbs…..

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