Genetic and biochemical heterogeneity of beta-thalassaemia in Naples

We have investigated 32 children with Cooley's anaemia from Naples, Italy. Criteria for inclusion in the study were: (a) typical clinical and haematological findings; (b) absolute transfusion requirement; and (c) elevated Hb A2 in both parents. From biosynthetic studies we have established that five children (including two sets of sibs) had beta-0 thalassaemia, while the rest had beta + thalassaemia. Thus, the frequency of beta + thalassaemia among unrelated patients was about 90%. The distribution of beta/alpha ratios among beta + patients ranged from 0.01 to 0.16 and it was bimodal, consistent with some of them having a beta-0/beta + genotype and others a beta +/beta + genotype. The distribution of beta/alpha ratios of the patients' parents (obligate heterozygotes) ranged from 0.24 to 0.73, and it was plurimodal, consistent with the coexistence in this population of multiple beta thalassaemia alleles, of which one must be beta-0 and at least one is beta +. A systematic analysis of 20 families indicates that the beta/alpha ratio is to some extent quantitatively inherited, and its suggests non-randomness in the assortment of beta thalassaemia alleles that can give rise to a Cooley's phenotype.