The heterogeneity of normal Hb A2-beta thalassaemia in Greece.
Nine patients have been observed with homozygous beta 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-beta thalassaemia in this group showed minimal red cell abnormalities, normal osmotic fragility but imbalanced globin chain synthesis (alpha/beta=1.6), and appear to correspond to previous descriptions of 'silent' beta thalassaemia. Double heterozygotes with high Hb A2-beta thalassaemia have a clinical picture of mild beta thalassaemia intermedia characterized by relatively low levels of Hb F (less than 20%) and gamma chain synthesis. Group 2 (three families). beta Thalassaemia heterozygotes with normal HbA2 levels in this group showed more marked red cell abnormalities, decreased osmotic fragility and more imbalanced globin chain synthesis (alpha/beta=2.5) than those in group I. Double heterozygotes with high Hb A2-beta thalassaemia are more severely affected and are transfusion dependent. Haemoglobin F and gamma chain synthesis are high in these cases. The frequency of normal Hb A2-beta thalassaemia in Greece may be as high as 10% of all beta 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.
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005817:Genetic Counseling; D005914:Globins / Q000096:biosynthesis; D006115:Greece; D006441:Hemoglobin A / Q000032:analysis*; D006443:Hemoglobin A2 / Q000032:analysis*; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D013789:Thalassemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
D005914:Globins; D006441:Hemoglobin A; D006443:Hemoglobin A2