Sá+ thalassaemia in Jamaica: haematological comparison of the three commonest á+ thalassaemia mutations

A study of the á-thalassaemia mutations by amplification refractory mutation system (ARMS) PCR of 130 Sá+ thalassaemia patients attending the sickle-cell clinic at the University of the West Indies revealed that 70 (53.9 percent) had the -29 (A to G) mutation, 23 (17.7 percent) had -88 (C to T), 19 (14.6 percent) had Poly A(AATAAA to AACAAA) and 2(1.5 percent) had C24 (T to A). In 16 (12.3 percent) patients we were unable to identify the mutations with the available primers. Of the three major groups, the -88 group had a higher foetal haemoglobin (HbF) than the -29 groups, who in turn had a higher haemoglobin (p<0.001). The -88 and -29 groups had a higher haemoglobin (p<0.01), a higher corrected haemoglobin A2(p<0.001), a higher calculated cell volume (p<0.001), a higher packed cell volume (p<0.01) and a higher mean cell volume (p<0.05) than the Poly A group. The -29 group also had fewer reticulocytes than the Poly A group (p<0.001). The difference in HbF levels could be a consequence of the thalassaemia mutations affecting the interaction of the á-globin gene to differing extents (AU)

Chromatographic quantitation of HbA levels for distinguishing genotypes of sickle-cell á+ thalassaemia - abstract

Sickle-cell á+ thalassaemia represents a spectrum of conditions, depending on the molecular basis of the á+thalassaemia gene. Different genes manifest different levels of beta chain synthesis and hence varying amounts of HbA. Different á+thalassaemia genes also characterise sickle-cell á+thalassaemia in different groups, several of which occur in Jamaica. Commonest among people of African ancestry are the -29 and -88 substitutions which result in a very mild sickle-cell á+thalassaemia type III associated with high HbA levels (18 - 25 percent). The Indian population manifests more severe genes causing sickle-cell, á+thalassaemia type II with 8 - 15 percent HbA and sickle-cell á+thalassaemia type I with 3 - 5 percent HbA. Estimation of the level of HbA is therefore useful in predicting the probable molecular basis for the á+thalassaemia gene and also the expected clinical course. Measurement of HbA by chromatography in sickle-cell á+ thalassaemia requires adequate separation from both HbS and HbF and anew method is presented which appears to give satisfactory results. The method is based on 0.5M Tris-5 percent acetic acid. Duplicate runs on blood samples from 28 patients gave mean (SD) values of 17.4 (6.7) and 17.2 (6.9) with between-run differences of 0.2 (95 percent C.I.,-0.7, 1.1) p = 0.65; 95 percent of the differences between runs were 4.7 percent or less. HbA measurements with this method did not allow the same grouping as in Greece, which may be due to differences in the two populations or to measurement error. The method is relatively simple and of considerably lower cost than high-performance liquid chromatography (HPLC) (AU)