Phenotypes of individuals with a beta thal classical allele associated either with a beta thal silent allele or with alpha globin gene triplication

Abstract

BACKGROUND AND OBJECTIVE: beta thalassemia intermedia has its origins in compound heterozygosity for many different beta thal defects or in an interaction of a beta thal defect with altered alpha cluster. Two specific genetic associations (beta thal/beta(+) -101 C-->T and beta thal + alpha alpha alpha or alpha alpha alpha alpha) have been described in recent years as being determining a phenotype similar to that of simple beta thal heterozygote or, alternatively, a clinical picture of thalassemia intermedia. METHODS: A detailed study on this subject was carried out on 55 patients divided into 2 groups. Group I consisted of 20 patients, 17 of whom (Group Ia) had a beta thal/beta(+) -101 C-->T genotype and 3 (Group Ib) had a beta thal/beta IVS II-844 C-->G genotype. Group II consisted of 35 patients with beta thal association + alpha alpha alpha or alpha alpha alpha alpha. The methods of study have already been described in a previous issue. RESULTS: Thirty percent of group Ia and 25% of group II were virtually asymptomatic, while the others presented the thalassemia intermedia phenotype. This second phenotype is generally milder in patients of group I and even less so in those of group II. In the former there is a higher level of HbF; in the second there is more marked alpha/beta + gamma globin synthesis imbalance. The severity of the phenotype has no connection with that of the beta thal defect. The patients of group Ib all presented thalassemia intermedia. INTERPRETATION AND CONCLUSIONS: The definite clinical pictures of groups I and II are quite common in the Italian population and should therefore be well understood, especially for proper application of preventive measures against thalassemia major.