Abstract
Thalassemia syndromes and unstable hemoglobins traditionally represent two phenotypically separate disorders of hemoglobin synthesis. Highly unstable hemoglobin variants, however, often have phenotypic characteristics associated with both ineffective erythropoiesis (thalassemias) and peripheral hemolysis (unstable hemoglobins). Many highly unstable β chain variants cause a dominant thalassemia-like phenotype, in which simple heterozygotes for such mutations have a clinical expression similar to thalassemia intermedia. The phenotypic expression of highly unstable α-globin variants is usually less severe, due mainly to a gene dosage effect, and they are often only characterized on interaction with other α-thalassemia mutations, whence they are classified as nondeletional α-thalassemia determinants. This study reports the clinical and hematological findings in five cases with rare α-thalassemia genotypes: a single patient with the thalassemic α2-globin gene codon 59 Gly→Asp hemoglobin variant in trans to an α+-thalassemia deletion, and four compound heterozygotes for the nondeletional α-thalassemia polyadenylation mutation (α2 gene AATXAA→AATAAG or aT-saudi α/-α) and an α+-thalassemia deletion. Evaluation of the clinical and hematological features in these two analogous genotypes clearly demonstrates the more severe clinical expression associated with the α-thalassemic unstable hemoglobin variant. In addition, the case in this study with the codon 59 α chain variant provides a further example illustrating the spectrum of phenotypes associated with the a-thalassemic hemoglobinopathies.