Genetic Patterns in Thalassemia Intermedia (Constitutional Microcytic Anemia)

Abstract

Globin chain synthesis has been studied in 17 patients with thalassemia intermedia, and their relatives, also investigated by routine hematologic and hemoglobinic tests. The mean α/non α ratio was always around 2.20–2.30. In patients with severe thalassemia major, used as a control, the mean α/non a ratio was significantly higher, that is 3.11–3.07. Therefore, the hypothesis that the cause of the lesser severity of the thalassemia intermedia is a lesser imbalance of globin chain synthesis, is suggested. One or both the parents of patients with thalassemia intermedia have mild β-thalassemia and normal α/βratio, whereas the parents of patients with severe thalassemia major show a marked β-thalassemia and a mean α/β ratio of 1.76. These data suggest that genes for β⁺-thalassemia are responsible for thalassemia intermedia, and genes for β°-thalassemia are responsible for thalassemia major. In two patients with thalassemia intermedia, the association of an α-thalassemia gene with homozygous β-thalassemia that it is well known to reduce the globin chain imbalance typical of the β-thalassemia, has also been observed.

<i>&beta;⁺</i>-Thalassemia Intermedia

“…According to their biological fea tures, our 3 subjects with /¿Mhalassemia in termedia do not belong to either of these groups. They are more similar to some forms of thalassemia intermedia described in Italy [Bianco et al, 1977;Gallo el al., 1979], which is not unexpected since the family is of Italian origin.…”

“…The study of globin chain synthesis in several Italian families has indeed shown that one or both parents of subjects with thalassemia intermedia often have a mild picture of /Mhalassemia heterozygote, with a normal or subnormal non-«/« biosynthetic ratio [Bianco et al, 1977;Gallo et al, 1979]. Sometimes, the presence of genes for a-thalassemia together with homozygosity for /?-thalassemia lead to a clinical pattern of thalassemia intermedia [Bianco et al, 1977;Gallo et al, 1979].…”

“…De scribed under the name of constitutional mi crocytic anemia in 1944fSilvestroni, 1944, it was integrated into the thalassemia syn dromes in 1964 [Pearson, 1964;Bunn et al, 1977]. Several groups of authors have since shown that thalassemia intermedia corres ponds to a variety of genetic disorders and arises in most cases from the combination of different thalassemia genes [Silvestroni et al, 1957;Aksoy, 1970;Bianco et al, 1977;Aksoy et al, 1978;Weatherall and Clegg, 1972], Recent studies have tried to corre late the lesser severity of thalassemia inter media to a lesser imbalance of globin chain synthesis [Bianco et al, 1977;Gallo et al, 1979]. This correlation is not, however, ob served in ali types of thalassemia intermedia [Cividalli et al, 1978], In order to obtain additional information on this question, we have examined, at the globin chain synthesis level, a family in which 3 subjects presented the clinical picture of thalassemia interme dia.…”

Molecular Analysis of Beta-Thalassemia and Sickle Cell Anemia in Antalya

“…The majority of the β-thalassemia intermedia patients had compound heterozygosity for IVSI-110 and IVSI-6 in our study, whereas the most frequently detected genotype among β-thalassemia intermedia patients was reported as IVSI-6/IVSI-6 in other studies [7, 8]. It is evident that the severity of the β-thalassemias is related to the degree of imbalance of the globin chains, and that thalassemia intermedia is caused by genes for β + -thalassemia, and thalassemia major is caused by genes for β-thalassemia [25]. It was reported that this may result from inheritance of a mild β-thalassemia mutation resulting in a residual β-chain output or reduction of α-chain synthesis due to co-inheritance of α-thalassemia or genetic interaction which results in increased synthesis of fetal hemoglobin [26].…”

Camperdown hemoglobin associated with beta° thalassemia in a Brazilian child

“…This is the first report of the co-occurrence of Hb Camperdown and b°-thalassemia. b-thalassemia heterozygotes manifest a typical clinical picture, characterized by mild anemia, reduction in mean cell volumes and in mean cell hemoglobin concentrations, elevated concentrations of HbA 2 , altered erythrocyte morphology, and imbalance of globin-chain synthesis with an alpha/beta ratio > 1 (Bianco et al, 1977). Hb Camperdown is considered slightly unstable, resulting in a benign clinical course in heterozygous individuals (Wilkinson et al;1975;Blouquit et al, 1984;Kister et al, 1989;Miranda et al, 1996).…”