The Heterogeneity of Normal Hb A2‐β Thalassaemia in Greece

Abstract

Nine patients have been observed with homozygous β thalassaemia in each of whom one parent has a normal level of Hb A₂. On the basis of clinical, haematological and globin chain synthesis studies these families have been divided into two groups. Group 1 (six families). Heterozygotes for normal Hb A₂–β thalassaemia in this‐group showed minimal red cell abnormalities, normal osmotic fragility but imbalanced globin chain synthesis (α/β= 1.6), and appear to correspond to previous descriptions of ‘silent’β thalassaemia. Double heterozygotes with high Hb A₂‐β thalassaemia have a clinical picture of mild β thalassaemia intermedia characterized by relatively low levels of Hb F (Group 2 (three families), β Thalassaemia heterozygotes with normal Hb A₂ levels in this group showed more marked red cell abnormalities, decreased osmotic fragility and more imbalanced globin chain synthesis (α/β=2.5) than those in group 1. Double heterozygotes with high Hb A₂‐β thalassaemia are more severely affected and are transfusion dependent. Haemoglobin F and γ chain synthesis are high in these cases.The frequency of normal Hb A₂‐β thalassaemia in Greece may be as high as 10% of all β thalassaemia genes and this poses a significant problem for genetic counselling. Various molecular mechanisms are discussed which could account for the heterogeneity within these disorders.