Alpha-thalassaemia trait in various racial groups in the United Kingdom: characterization of a variant of alpha-thalassaemia in Indians.

Patients whose red-cell indices are suggestive of thalassaemia trait, but who have a normal haemoglobin electrophoretic pattern, may be carriers of alpha-thalassaemia. A diagnosis of alpha-thalassaemia 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 haemoglobin. Patients with alpha-thalassaemia 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 haemoglobin H(Hb H) preparation was assessed in proven alpha-thalassaemia heterozygotes of various races. A high proportion of 'false negative' results in Indian and Negro heterozygotes indicated that the Hb H preparations 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-thalassaemia heterozygotes (2.0+/0SD 0.6) compared with that of the control group (2.1+/0SD0.5). Comparison of data from patients with alpha- and beta-thalassaemia traits showed that alpha-thalssaemia trait is the milder disorder, in terms of its effects of red-cell morphology, red-cell indices and degree of globin chain imbalance. Amongst individual patients with alpha-thalassaemia trait, there was no correlation between the alpha/beta specific activity ratio and the red-blood-cell(RBC) d the red-blood-cell (RBC) count, mean corpuscular volume (MCV) and mean corpuscular haemoglobin (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 sutdy to characterize alpha-thalassaemia trait in Indians, in whom it appears to be a common disorder. Haematologically, alpha-thalassaemia trait in Indians is milder than that seen in Chinese and the fact that haemoglobin Bart's hydrops fetalis does not occur in Indians makes it likely that the genetics of Indian alpha-thalassaemia differ from those of the Chinese disease. A possible genetic model for Indian alpha-thalassaemia is discussed and the identification of the homozygote is seen as the first step in the determination of the underlying molecular defect.