Thalassaemia of intermediate severity resulting from the interaction between alpha- and beta-thalassaemia.

Abstract

SUMMARY A Sicilian family is described in which the a-thalassaemia gene is interacting in several members with fl-thalassaemia resulting in a balanced l/f chain production ratio. In one patient, affected by homozygous fl-thalassaemia, the presence of a-thalassaemia resulted in a less severe clinical expression of the disease, less marked imbalance in the a/non-a ratio, and a lower level of Hb F. Further studies of haemoglobin synthesis are needed to clarify the complex genetic picture that results from the interaction of different forms of thalassaemia.The term 'thalassaemia intermedia' is used to describe those forms of thalassaemia of intermediate clinical and haematological severity between thalassaemia major and asymptomatic carriers. These forms are a genetically heterogeneous group which usually result from the interaction between 2 different thalassaemia genes, or else from the combination of ,-thalassaemia with genes responsible for structural anomalies of the globin . In particular, it has been observed that the interaction between a-and ,B-thalassaemia gives a less severe clinical picture than homozygous ,-thalassaemia (Kan and Nathan, 1970). In the case reported by Kan and Nathan, one of the parents was a carrier of f-thalassaemia with characteristic alteration of red cell morphology, high Hb A2, and unbalanced synthesis of a and , / chains. The other parent, though presenting the morphological appearance off,-thalassaemia, with increased Hb A2, had a balanced a/fl? synthetic ratio. Kan and Nathan concluded that in the propositus the presence of the athalassaemia gene could modify the clinical manifestation of the disease, with normal survival and minimal clinical symptoms. The propositus showed, in fact, slight enlargement of the liver and spleen, and his haemoglobin ranged from 9 to 11 g/dl. He seldom needed blood transfusions.There are 2 forms of a-thalassaemia trait: one without alteration of red cell morphology (a-thalassaemia 2) and only slight imbalance of the a/l ratio,

Identification of a novel β0 ‐ thalassaemia mutation in a greek family and subsequent prenatal diagnosis

“…[-a globin gene cluster showed that the proband and his parents are heterozygous for the rightward single a-globin gene deletion ( -~~'~/ a a ) (data not shown). This may be significant, since concomitant a-thalassaemia can meliorate the clinical severity of homozygous p-thalassaemia (Kan and Nathan, 1970;Musumeci et al, 1978;Loukopoulos et al, 1978;Weatherall et al, 1981). However, this effect is usually associated with genotypes consisting of two p+thalassaemia mutations or the combination of a particularly mild P+-thalassaemia mutation and a $-thalassaemia mutation.…”

Unusual combination of genetic defects in a Sicilian boy: Gγ Aγ δβ thalassemia, Gγ Aγ heterocellular HPFH, βº thalassemia, and albinism

“…It has been seen that gene expression can be influenced by the presence of other genetic or acquired anomalies [Musumeci et al, 1978;Nute et al, 1978;Weatherall et al, 19811. It has been repeatedly reported that the simultaneous presence of heterocellular HPFH or a thal plus homozygous thal or homozygous Hb S made these forms unusually mild [Musumeci et al, 1978;Dubart et al, 1980;Prchal et al, 1981;Cappellini et al, 1981;Marinucci et al, 1981;Weatherall et al, 19811. Nute et a1 [I9781 demonstrated that reduction of hemoglobin synthesis, due to an acquired condition such as iron deficiency, reduces erythrocytosis in subjects with hemoglobin Olympia.…”