The drepanocytic anaemia is a native disease of the African countries where the healthy carriers are even the 25% of the population. At smaller frequencies, it is also present in Italy and today tends to increase following the increasing immigration of population coming from the African continent. It is characterized by the presence of the sickle cell anaemia (or drepanocytosis or Hb S) and that is, by a mutation of the β globin gene giving arise to an anomalous haemoglobin.
As the thalassaemia, also the sickle cell anaemia involves in the hereditary transmission as an autosomal dominant Mendelian character.
In heterozygotic condition, the sickle cell mutation does not give disease place: the carrier is healthy.
The drepanocytic anaemia (or sickle cell anaemia) is the disease caused by the homozygotic condition of the gene for the Hb S (βS/βS).
Biochemical and functional characteristics of the HbS
The structural alteration typical of the βS globin chain is the substitution, in the position 6, of this chain of a acid glutammic residue with a valine one.
As consequence of this mutation, the Hb S mobility, in electrophoresis at alkaline pH, is a great deal smaller than that of the HbA.
In drepanocytic anaemia patients, it is only present the HbS, further to a modest HbF level and a normal HbA2 one. In the microdrepanocytic disease, the patient constantly shows a HbA2 level in the β thal range, a predominant HbS level and a more modest of HbF amount, but in some cases (as when the patient is a β+ thal carrier) also a small HbA.
Under oxygen-deficiency conditions, the erythrocytes, containing HbS, manifest a fundamental property quickly appearing slightly curved and lengthen characterized by numerous, long thread-like prolongations that depart from the two extremities of the cell.
The erythrocytes strongly become alike to so many falces, from which the names of sickle cell anaemia or drepanocytosis.
The process of deformation is caused by the polymerization phenomenon of the βS chains within the erythrocyte. Long bundles of fibers constituted by Hb S polymers, the tactoids arrange through intertetramer contacts between a projection and a hydrophobic pocket situated in specific βS globin chain positions, assuming these parallel orientations along the erythrocytic long axis. Contemporarily to the sickle phenomenon, the Hb S aggregates affecting its solubility and leading to rapid gel formation.
Clinical features of the drepanocytic anaemia (homozygosis for the gene of the Hb S: βS/ βS)
The drepanocytic anaemia shows a more or less severe normochromic anaemia picture that can be diagnosed through the haemoglobin study evidencing the Hb S presence. Overall, in blood samples incubated at 37°C under conditions of anoxemia, within few times, the sickle deformation of many erythrocytes appears. The clinical picture is characterized by sudden painful, violent and recurrent crisis, that can appear since the first years of life and that have various location: bony, articulate and muscular; or visceral, pulmonary, abdominal.
Various neurological manifestations and frequent cerebral ictus can rise up. All these affections are caused by thrombosis and infarction as consequence of massive sickling distortion of erythrocytes in circle.
The course of the disease is partly regulated by the Hb F amount present in the patient: it is lighter if this level is higher and vice versa. In the African countries, particular haplotypes were found out putting in evidence that the presence of the Gγ -158 C→T mutation results in a higher Hb F of patient and therefore in a slight severe disease.
The Senegal haplotype, including this mutation, causes a relatively light disease, while the haplotype Bantu, not including it, is associated with a more severe disease.
The anatomo-pathological finds are characterized in both the diseases by a predominant presence of thrombosis, heart attacks, voluminous sequestrations in various organs due to the great difficult circulation of the sickle erythrocytes.
