SUMMARY The frequency of thalassaemia syndromes in Sardinia was examined by a population survey. The data indicate that about 12.6% of the Sardinian subjects are carriers of,B-thalassaemia, while 6.9% of the population carries an -thalassaemia gene, with a slight difference between the various provinces. These are among the highest frequencies of thalassaemia genes found in a Caucasian population today.A survey of hospital inpatients and outpatients showed a newborn incidence of homozygous ,6-thalassaemia of 1 in 300. The reasons for the difference between the expected and observed incidence figures are discussed. Moreover, 3 subjects with 5,f-thalassaemia trait, 6 carriers of heterocellular persistence of fetal haemoglobin (HPFH), 1 sickle cell trait, and 3 subjects with Hb J Sardegna were found.Genetic heterogeneity of fJ-thalassaemia syndromes in this population may generally result from the interaction of a-and fl-thalassaemia genes.The incidence and distribution of thalassaemia syndromes in Sardinia have been previously investigated (Silvestroni and Bianco, 1960;Carcassi, 1963;Siniscalco et al., 1966

In this article we report a Sardinian family, in which a beta- thalassemia gene and a triple alpha-globin loci, counterpart of the rightward deletion type alpha-thalassemia-2, were segregating. The analysis of the genotype-phenotype correlations in the different family members allowed us to give an outline of the manifestations associated with different genotype combinations. The heterozygote for the triple alpha-loci showed no consistent abnormal clinical or hematologic characteristics and presented balanced alpha/beta-globin chain synthesis. In the homozygous state for this lesion, the only phenotypic expression was a slightly imbalanced globin chain synthesis. The combination of heterozygous beta-thalassemia with the heterozygous state for the triple alpha-globin loci produced no clinical manifestations and showed a hematologic phenotype indistinguishable from that of heterozygous beta-thalassemia. On the other hand, the combination of the homozygous state for the triple alpha-globin gene loci and the heterozygous state for beta-thalassemia produced a clinical picture of thalassemia intermedia with a very mild clinical course, minor increase of fetal hemoglobin (HbF) levels, and a pronounced imbalance of globin chain synthesis.

The red cell indices and results of globin chain synthesis in peripheral blood of obligate beta 0 thalassemia (beta 0 thal) carriers (parents of homozygous beta 0 thal children) and beta thalassemia (beta thal) carriers identified during mass screening are reported. Red cell indices were similar in obligate beta 0 carriers and in carriers diagnosed during mass screening. However there was a higher incidence of anemia in female obligate beta 0 thal carriers. In Sardinia the beta 0 thal carrier showed the usual hematological characteristics of the high Hb A2 beta thal carrier with microcytosis, hypochromia, reduced osmotic fragility; Hb F greater than 1% was found in 30% of the carriers. With MCV, MCH, osmotic fragility test (OFT) and Shine and Lal discriminant function we found 3.5%, 1.5%, 3.5% and 4.0% respectively false negatives in carrier identification. A part from one subject, all obligate carriers had elevated Hb A2 levels. The alpha/beta ratio in obligate carriers (mean +/- SD) was 1.83 +/- 0.26 (N = 30).

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In this study we describe the correlation between the haematological parameters (red cell indices and Hb Bart's levels) and the alpha-globin genotype in Sardinian newborns. Increased Hb Bart's levels at birth always indicates alpha-thalassaemia, either of the deletion or non-deletion variety. Infants with two alpha-globin genes deleted (- alpha/- alpha and --/ alpha alpha genotypes) had microcytosis, low MCH and Hb Bart's in the 2.0-7.1% range. A minority (38.9%) of infants with the (- alpha/ alpha alpha) globin genotype had detectable Hb Bart's, in the 0.78-2.5% range, frequently associated with minimal microcytosis while the remainder (61.1%) were completely silent. Infants carriers of a non-deletion type of alpha-thalassaemia showed Hb Bart's levels within the range found in the (- alpha / alpha alpha) genotype. The association of heterozygous beta 0-thalassemia seems to have no effect on the expression of any of these alpha-thalassaemia lesions at birth.