Trimodal distribution of HbS levels in sickle heterozygotes - An useful predictor of the alpha-genotype for population screening

The trimodal distribution of HbS levels in sickle heterozygotes has been us ed as an indirect approach to determine the prevalence of alpha-thalassaemi a in different population groups. We used this approach to predict the alph a-genotypes of 124 sickle cell heterozygotes where the HbS concentration va ried from 20 to 46 per cent with antimodes at 28.0 and 33.0. The alpha-geno types in these individuals were also determined by Southern blot hybridizat ion. We predicted homozygous (-alpha/-alpha) or heterozygous (-alpha/alpha alpha) alpha-thalassaemia-2 in 78 subjects by the trimodal distribution of HbS. However, actual genotyping showed that 75 patients had a-thalassaemia. Forty six of the 47 subjects with a normal alpha-globin genotype (alpha al pha/alpha alpha) could be predicted indirectly. The overall sensitivity was 100 per cent and specificity was 94.2 per cent with a positive predictive value of 96.2 per cent and negative predictive value of 100 per cent. As al pha-genotyping is very expensive and not feasible in most laboratories in I ndia, we conclude that the trimodal distribution of HbS levels is a suitabl e method for screening for alpha-thalassaemia in population studies.