Screening for the beta-thalassaemia trait: hazards among populations of West African Ancestry

Abstract

The aim of this study was to examine the accuracy and characteristics of detecting the beta-thalassaemia trait in populations of West African ancestry. School children, aged 16-19years, in Manchester Parish, Jamaica were screened to detect the genes which could give rise to offspring with sickle cell disease. Haematological indices and HbA(2) levels in subjects with an MCH ≤ 26pg and an RDW < 18.0 with DNA analysis in those with indices consistent with the beta thalassaemia trait were measured. The performance of published discriminant indices in distinguishing iron deficiency and beta-thalassaemia trait in this population was assessed. Of 10,148 subjects, 1,739 (17.1%) had an AA haemoglobin phenotype and red cell indices consistent with beta-thalassaemia (MCH values ≤ 26pg, RDW < 18.0) requiring estimations of HbA(2) levels. HbA(2) levels were ≥3.5% in 112 and beta-thalassaemia mutations were identified in 77 of these including the -88 C>T mutation in 35 (45%), -29 A>G in 19 (25%), -90 C>T in 7 (9%), the IVS II-849 A>G in 5 (6%) with smaller contributions from five other mutations. Discriminant indices performed poorly in the differentiation of iron deficiency and the beta-thalassaemia trait. Detection of the beta-thalassaemia trait is relatively insensitive in populations of West African ancestry partly because of the mild defects characterising beta-thalassaemia in this population and also the high prevalence of deletional alpha thalassaemia. More sensitive indicators are required for beta-thalassaemia detection to inform such populations at risk of offspring with sickle cell disease.