Haematologica 2002; 87:(12)ELT44
[Medline] [prev] [index] [next]The prevention of thalassemia major: emerging problems
Maffei L, Foglietta E, Cappabianca MP, Lerone M, Mastropietro F, Bianco I
Associazione Nazionale per la lotta contro le Microcitemie in Italia, Centro Studi della Microcitemia di Roma, via Galla Placidia 28/30, 00159 Rome, Italy
The study of 84 compound heterozygous thalassemics with b thal/b thal silent or b thal + aaaanti 3.7 (triplicated a gene) shows a very marked variability in the severity of their clinical pictures and a high number of silent phenotypes (respectively 71% and 33%).
In the examined population, the high frequency of aaaanti 3.7 carriers among the healthy partners of b thalassemics is indicative of the necessity to routinely search for triplication or quadruplication of the a gene and of the b thal silent mutations, in these subjects.
The clinical pictures of the compound heterozygotes for an evident b thal gene and a silent b thal gene or for an evident b thal gene and the triplication of an a globin gene have been illustrated1-7 in the last decade in isolated cases or in small groups of subjects who showed a phenotype like that of an evident or severe b thal intermedia, but often that of simple b thal heterozygosis.
In a recent paper8 we described 17 compound heterozygotes for b+ -101 C->T and b thal who showed the hematologic picture of simple b thal heterozygotes (29%) and that of never severe b thal intermedia patients (71%). Another 35 subjects, compound heterozygotes for b thal and triplication of the a globin gene, showed the picture of healthy b thal carriers (27%) and that of an evident or severe b thal intermedia (75%). In both the groups splenomegaly was almost always modest (2-3 cm under the rib cage). Analyzing these data we face the important question of suggesting interruption of a pregnancy, in case of fetal compound heterozygousis for these defects. The problem's lead us to extend the research to reach two objectives: first, to collect complete and documented information about different clinical and hematologic severity of these diseases to give couples at risk the widest and the most documented material for deciding whether to apply an intervention or not. Second we had to plan a strategy and put it into action quickly to identify b silent thal or aaaanti 3.7 or aaaanti 3.7 carriers, among apparently healthy partners of b thalassemics.
Our first objective the fact that numerous people pour into our Center (the only one in Latium specialized to study thalassemias), not only from Rome but from all the Regions of Central and Southern Italy and also recently from many other Mediterranean Countries. It is there which the frequency of the non-a thalassemias is higher than in the general population (10.9% vs. 2.2%). In the last three years we have selected, not only the well recognizable b thal intermedia cases, but also subjects who only had the picture of an evident heterozygous b thal. Through this identification we discovered 4 more cases of compound heterozygosis b thal/b thal: 101 C->T, and 28 more new cases (belonging to 15 families) of compound heterozygosis b thal + aaaanti 3.7 (which are probably not all those existing in the population). All these cases have been definitely diagnosed by the study of the globin genes' DNA.
Adding the previous data to the present ones, results that we consider definitive, we show the different severity of expression of the phenotype of these b thal int that go from the picture of a simple heterozygous thalassemic to that of a mild or evident b thal int patient, and present their different frequencies.
The most relevant datum resulting from these observations is the very high frequency, in both groups, of sub-silent or completely silent cases. They are always compatible with an almost normal quality of life (respectively 71% in the compound heterozygosis b thal /b -101 C->T and almost 33% in the compound heterozygosis b thal + aaaanti 3.7) and would be at risk, in the absence of the necessary exams, of being confused inside the large group of the thalassemic heterozygotes without receiving the right diagnosis and necessary care. Instead the very serious patients (4 in our collection) are b thal heterozygotes and aaaanti 3.7 homozygotes always described in literature,4,5,9 or b thal heterozygotes and aaaanti 3.7.
To reach the second objective, from February 2001 to October 2002, we examined 447 completely normal partners (that is, also excluding those with very mild thalassemic characters) of b thal subjects and among them we found (Table 1-2) a high frequency of aaaanti 3.7 carriers and a low frequency of b thal -101 C->T heterozygotes. This datum suggests routinely including diagnostic examination to be performed in all the strongly thalassemic countries, to prevent thalassemic disease, search for all the silent b thal and triplication or quadruplication of an a globin locus in the apparently healthy partner of b thalassemics. We also suggest performing this research in couples at risk in which both partners have been diagnosed to be a carrier of an evident b thalassemic defect.
In our opinion the two varieties of compound b thalassemic heterozygosis that we have described are, after the H hemoglobinosis, a new example of thalassemic conditions that extends outsideout of the canonical limit of prenatal diagnosis and selective abortion and required different solutions.References