Type II will be described first as it is the most common type of CDA. It is transmitted as an autosomal recessive disease; the geographical distribution of the earlier recorded cases suggests a particularly high frequency in north-west Europe, in Italy and in North Africa. It is usually diagnosed in the first few years of life.
Some cases have presented with anaemia and/or jaundice at birth, and this should be considered in the evaluation of nonimmune hydrops fetalis. The clinical manifestations include a variable degree of jaundice, hepatomegaly and splenomegaly, cirrhosis, and diabetes, even in patients who have neither been transfused nor treated with iron. A few patients have been mentally retarded. The serum iron and transferrin saturations are increased.
Type II has an eponym, 'Hempas' - hereditary erythroblast multinuclearity with positive acidified serum - because of the unique feature that the red cells are haemolysed by some acidified normal sera but not by the patient's own serum, unlike PNH. In Hempas, there is a specific antigen on the erythrocytes, which reacts with an lgM anti-Hempas antibody present in the sera of about 30% of normal people in sufficient amounts to cause lysis. This susceptibility to lysis is probably due to abnormal complement control resulting from a defect in the complement-regulating protein glycophorin A (see below).
In common with other types of dyserythropoiesis, there is enhanced I and i antigen activity, demonstrated in vitro by increased agglutination and by a positive cold-antibody (anti-I) lysis test.
Type II shows the abnormal features described above. In addition, there is a characteristic peripheral arrangement of endoplasmic reticulum giving the appearance of a 'double membrane' (Figure 13.8).
Pathogenesis appears to be an enzymatic defect in the glyco-sylation pathway leading to abnormalities in glycoprotein bands 3 and 5.5 and glycophorin A. Two different enzyme defects have been identified, namely deficiency of alpha-mannosidase II and N-acetylglucosaminyl transferase II.
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