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

Indian J Med Res. 1998 Dec:108:285-90.

Abstract

The trimodal distribution of HbS levels in sickle heterozygotes has been used as an indirect approach to determine the prevalence of alpha-thalassaemia in different population groups. We used this approach to predict the alpha-genotypes of 124 sickle cell heterozygotes where the HbS concentration varied from 20 to 46 per cent with antimodes at 28.0 and 33.0. The alpha-genotypes in these individuals were also determined by Southern blot hybridization. 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 alpha-thalassaemia. Forty six of the 47 subjects with a normal alpha-globin genotype (alpha alpha/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 alpha-genotyping is very expensive and not feasible in most laboratories in India, we conclude that the trimodal distribution of HbS levels is a suitable method for screening for alpha-thalassaemia in population studies.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / diagnosis
  • Anemia, Sickle Cell / genetics
  • Child
  • Female
  • Genetic Testing*
  • Genotype
  • Hemoglobin, Sickle / genetics
  • Hemoglobin, Sickle / metabolism*
  • Heterozygote*
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prevalence
  • alpha-Thalassemia / blood*
  • alpha-Thalassemia / diagnosis
  • alpha-Thalassemia / epidemiology
  • alpha-Thalassemia / genetics

Substances

  • Hemoglobin, Sickle