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 betathalassaemia trait in populations of West African ancestry. School children, aged 16-19 years, 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≤26 pg 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 betathalassaemia 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 betathalassaemia (MCH values≤26 pg, 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.