L'emoglobina normale lenta A2: suoi rapporti con una nuova frazione emoglobinica lenta, B2, e sua importanza per il riconoscimento di varianti talassemiche che compaiono nelle famiglie di portatori di Thalassemia media e di emoglobinopatia H

Abstract

SUMMARY: 1) An increase of hemoglobin A₂ over 3% is regarded as one of the two fundamental manifestations of the commonest thalassemic mutant in the heterozygous condition i.e. thalassemia minima or typical microcytemia (here indicated as MA), while the other element is represented by the characteristic ensemble of the morphological and functional alterations of the erythrocytes. This assumption is based on the fact that the infrequent cases of sharp dissociation between the two elements i.e.i) red cells normality with A₂ above 3 % (mA), and ii) microcytemia with normal levels of A₂ (Ma). run in families and cannot be easily explained as a partial manifestation of a typical microcytemic gene.2) The unilocal origin of the Ma variant seems to be well proved by the segregations from 5 Ma × ma (normal) matings where 10 Ma and 9 ma children have been observed. Moreover this variant has been detected among the relatives of a carrier of Hb H, born from a Ma × ma mating. This is in agreement with other recently published reports and strongly suggests that the relationship between Hb H and atypical microcytemia (with low A₂) has a precise etiological significance.3) The unilocal origin of the mA variant (normocytic thalassemia?) is at the moment less firmly established. However a family is described (mating mA × MA) where the father and one child show the same mA phenotype; moreover one other child is affected by constitutional microcytic anemia (Th. media). This finding supports the observations of Silvestroni and Bianco, who have already reported that a number of patients with intermediate thalassemic syndromes are born from mA × MA matings.4) At the moment no data exist which enable to decide whether the different thalassemias are mutations of the same or of different loci; however if they shall be shown to be allelic, the hypothesis must be kept in mind that the Thalassemia locus is a complex locus with more than one mutation sides, responsible for different but correlated aspects of the phenotype (red cell structure and A₂ level).5) The new hemoglobin B₂, is described which has been recently identified by Kunkel. Ceppellini, Dunn and Firsheim (unpublished data). Reasons are given for regarding B₂ as the product of a mutation at the locus which is responsable for the synthesis of A₂ (locus Hb₂), The relationship of allelism between A₂ and B₂ is a proof of the genetic heterogeneity of the hemoglobin of the normal adult and may be taken as a model suggesting the genetic heterogeneity of hemoglobin A, notwithstanding its apparent chemical omogeneity.6) It is concluded that the conditions generally indicated as Thalassemias represent a genetically heterogeneous group, which have nonetheless to do with related metabolic processes. It is therefore suggested that the term Thalassemia may be mantained for indicating all hereditary defects which directly interfere with hemoglobinogenesis although not producing a specific abnormal hemoglobin.