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Thalassemia (Thal) is an inherited blood disorder endemic to the Mediterranean and Middle East (e.g., KSA and UAE). This disease is caused by defects in the synthesis of one or more hemoglobin chains in red blood cells (RBCs). Alpha (α) Thal is caused by a reduced or absent alpha globin segment. Similarly, beta (β) Thal is caused by a defect in the beta globin segment. We divided the diseases into four groups: α Thal trait, α Thal disease, β Thal trait, and β Thal disease. The α or β Thal traits are milder variants of these diseases and do not require treatment; but β Thal disease (and to a lesser extent, α Thal) causes hemolytic anemia, splenomegaly, and bone deformities and requires repeated lifelong blood transfusions. This paper presents results regarding the identification of Thal variants using fluorescence spectroscopy of blood biomolecules and atomic force microscopy analysis of the morphologic features of red blood cells. The combined results provide new insights into the characteristics of these diseases. Furthermore, this study shows why β Thal disease subjects are often transfusion-dependent, and α Thal disease subjects are only occasionally transfusion dependent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

During a study of the molecular basis for severe forms of beta thalassemia in Sri Lanka, 2 patients were found to be heterozygous for beta thalassemia mutations. Further analysis revealed that one of them has a previously unreported molecular basis for severe thalassemia intermedia, homozygosity for quadruplicated alpha globin genes in combination with heterozygous beta thalassemia. The other is homozygous for a triplicated alpha globin gene arrangement and heterozygous for beta thalassemia. Their differences in clinical phenotype are explainable by the interaction of other genetic factors and, in particular, their early management. The clinical course of the 2 propositi underlines the importance of full genotyping and a long period of observation before treatment is instituted, particularly in patients with beta thalassemia intermedia associated with extended alpha globin gene arrangements. The hemoglobin (Hb) F levels in these patients with severe beta thalassemia intermedia, compared with other forms of this condition in the Sri Lankan population and elsewhere, are unusually low, a consistent finding in extended alpha globin gene interactions and in dominant beta thalassemia, raising the possibility that increased levels of HbF production in beta thalassemia may require mutations at both beta globin gene loci.