Clinical and molecular correlations in the sickle/β+‐thalassemia syndrome

Abstract

Sickle/β thalassemia is a sickling disorder of varying severity which results from compound heterozygosity for sickle cell trait and β‐thalassemia trait. Clinical and genetic studies have shown an inverse correlation between the level of hemoglobin A and the severity of the disease. It has been suggested that the level of hemoglobin A may be a function of the severity of the β‐thalassemia defect. In this study, we use molecular biological techniques to test this hypothesis. We show that the interaction of the mildest of the β⁺‐thalassemia genes with the sickle gene results in a high level of hemoglobin A. However, the interaction in this case resulted in a severe sickling disorder in the absence of significant anemia. We hypothesize that a mild β⁺‐ thalassemia gene may have two opposite effects on the clinical course of sickle/β⁺ thalassemia: (1) A high level of hemoglobin A which probably confers a favorable antisickling effect and (2) decreased hemolysis leading to increased numbers of total circulating red cells, thereby increasing the blood viscosity and the propensity for sickling. The inheritance of heterozygous α thalassemia 2 in conjunction with the mild β⁺‐thalassemia gene and sickle gene in this patient may have further enhanced the latter effect and resulted in a severe sickling disorder.