Alpha-Thalassaemia Trait in Various Racial Groups in the United Kingdom: Characterization of a Variant of Alpha-Thalassaemia in Indians

Abstract

Patients whose red-cell indices are suggestive of thalassemia trait, but who have a normal Hb electrophoretic pattern, may be carriers of .alpha.-thalassemia. A diagnosis of .alpha.-thalassemia trait was made in 44 such patients, using the incorporation of [3H]leucine by reticulocytes to measure the relative rates of synthesis of the .alpha.- and .beta.-chains of adult Hb. Patients with .alpha.-thalassemia trait had a reduced rate of synthesis of the .alpha.-chains, with a mean .alpha./.beta. specific activity ratio of 0.79 .+-. SD 0.07. The mean .alpha./.beta. specific activity ratio of 20 control subjects was 1.06 .+-. SD 0.08. The diagnostic value of the Hb H preparation was assessed in proven .alpha.-thalassemia heterozygotes of various races. A high proportion of false negative results in Indian and Negro heterozygotes indicated that the Hb H preparation is a highly unreliable screening test for use in a multi-racial population. There was no significant difference in the mean level of Hb A2 in .alpha.-thalassemia heterozygotes (2.0 .+-. SD 0.6) compared with that of the control group (2.1 .+-. SD 0.5). Comparison of data from patients with .alpha.- and .beta.-thalassemia traits showed that .alpha.-thalassemia trait is the milder disorder, in terms of its effects on red-cell morphology, red-cell indices and degree of globin chain imbalance. Among individual patients with .alpha.-thalassemia trait, there was no correlation between the .alpha./.beta. specific activity ratio and the red-blood-cell(RBC) count, mean corpuscular volume (MCV) and mean corpuscular Hb (MCH). This suggests that the .alpha./.beta. ratio cannot be used to distinguish between carriers of a mild gene (silent carriers) and carriers of a more severe disease. This is the first study to characterize .alpha.-thalassemia trait in Indians, in whom it appears to be a common disorder. Hematologically, .alpha.-thalassemia trait in Indians is milder than that seen in Chinese and the fact that Hb Bart''s hydrops fetalis does not occur in Indians makes it likely that the genetics of Indian .alpha.-thalassemia differ from those of the Chinese disease. A possible genetic model for Indian .alpha.-thalassemia is discussed and the identification of the homozygote is seen as the 1st step in the determination of the underlying molecular defect.