Introduction to Abnormal Heritable Haemoglobins PDF

Introduction to abnormal heritable haemoglobins GAVIN KNIGHT  Learning Objectives On completion of this session, you should be able to: 1. Differentiate between quantitative and qualitative structural haemoglobin defect 2. Compare and contrast α- and β- thalassaemia subtyp...

Introduction to abnormal heritable haemoglobins GAVIN KNIGHT  Learning Objectives On completion of this session, you should be able to: 1. Differentiate between quantitative and qualitative structural haemoglobin defect 2. Compare and contrast α- and β- thalassaemia subtypes  Heritable Haemoglobin variants Haemoglobinopathi es Quantitative defect Qualitative defect (amount) (quality) Reduced synthesis of normal Structural globin chains variants Thalassaemias HbS Hb Hb HbE C D α β δβ γδβ Glu-6-Val Glu-6-Lys Glu-121-Gln εγδβ Glu-26-Lys Alpha-Thalassaemia Normal α α α α Carrier α α Asymptomatic No symptoms α α α-thal minor α α or α α Mild microcytic anaemia α α α α HbH disease α α Symptomatic, microcytic anaemia. Splenomegaly. α α Hydrops foetalis. α α Incompatible with life α α Beta-Thalassaemia β Normal β Minor β β Asymptomatic β β No symptoms Intermedia Mild β β anaemia/splenomeg β β aly Major Anaemia, β hepatosplenomegaly β Growth retardation Thalassaemias Β Thalassaemia Genotype Clinical features Carrier (formerly β/β+, β/0 Normal to mild anaemia trait) No organomegaly Intermedia β+/β+, β+/β0 Mild anaemia Hepatosplenomegaly Major β0/β0 Anaemia Hepatosplenomegaly Growth failure/retardation αThalassaemia Genotype Clinical features α-thal carrier αα/-α Asymptomatic -α/-α or αα/-- HbH disease -α/-- Moderate to severe haemolytic anaemia. moderate ineffective erythropoiesis. Splenomegaly. Variable bone changes. Hb Barts/hydrops --/-- Incompatible with life Consequences of α4 deletion https://ashpublications.org/blood/article/91/7/2213/261092/Hydrops-Fetalis-Caused-by-Thalassemia-An-Em Summary  Haemoglobinopathy is a term used to describe abnormal haemoglobins  Although many haemoglobin variants are clinically silent, pathological variants affect oxygen carrying capacity, haemoglobin solubility or red cell life span  Thalassaemia describes conditions involving globin chain imbalance  Depending on the mutation clinical severity is variable  At their most extreme, the severity of thalassaemias can range from clinically silent to incompatible with life