The Unstable Haemoglobins A range of VERY rare

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

A brief recap – beta thalassaemia Minor Major • One malfunctioning/absent gene • reduced production of beta chains • surplus production of alpha chains • well compensated • Hb A 2 a 2 d 2 • Two malfunctioning/absent genes • No production of beta chains • surplus production of alpha chains • which precipitate on cell membranes • haemolysis & inefficient haemopoesis • haemopoetic hyperplasia

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

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

Meanwhile in Indianapolois Hb Indianapolis b 112 cys --> arg Very unstable b chain Very unstable haemoglobin precipitates just like in thalassaemia

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 β 110 leu → pro Hb Shanghai β 131 gln → pro

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

And other unstable Hbs…. . Frame Shifts Hb Stara Zagora β 137 – 139 -6 bp Hb Nijkerk β 138 - 139 +1 bp

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 Hb Zurich Albisrieden a 35 ser → pro a

And other unstable Hbs…. . Fusion Globin Hb Lepore Xanthi d 17 / β 22 fusion

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