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Hb C is another haemoglobin variant that is common in West Africa. Here the 6th amino acid of the beta chain (glutamic acid, negative charge) is not replaced by a valine but by a lysine (positive charge, basic amino acid), i.e.: (ß6 Glu->Lys) mutation. Sickling does not occur. Haemoglobin C has no protective effect on P. falciparum infection. The heterozygote state for Hb C is clinically silent. The peripheral blood contains 5-30% of target cells. By electrophoretic analysis, 30-40% of the haemoglobin is Hb C and 50-60% is Hb A. People who are homozygous for Hb C (Hb CC) display mild chronic haemolysis, mild to moderate anaemia and mild splenomegaly. On electrophoresis Hb A is absent. A relatively high percentage of Hb F (up tot 22%) is present in individuals having coexistent Hb CC disease and alpha thalassemia. Reticulocyte counts are slightly elevated (2-6%). There is often microcytosis and there are many target cells and some spherocytes. Cholelithiasis is common. Red blood cells may contain Hb C crystals. These intracellular crystals are more pronounced after overnight incubation in 3% sodium chloride. For an unknown reason, the interior of the red blood cells are slightly acidic. There are rarely major complications. Treatment is not necessary.
Hb D is the name for a number of abnormal haemoglobins that migrate a similar distance to Hb S in standard haemoglobin electrophoresis at pH 8.6. Therefore, Hb D can be confused with Hb S on standard electrophoresis with an alkaline pH. It is distinguished from Hb S by its normal solubility, an electrophoretic mobility on agar gel at an acid pH that differs from Hb S (e.g. citrate agar gel with a pH of 6.2), and its failure to produce sickling. The electrophoretic and solubility properties of Hb G are very similar to those of Hb C and the two are rarely differentiated. The heterozygote state for Hb D is clinically silent, but the condition can be mistaken for sickle cell trait. In the homozygous state, some cases are asymptomatic and others have a discrete haemolytic anaemia and mild to moderate splenomegaly. This is mainly the case for Hb DPunjab (ß121 Glu->Gln). This haemoglobin will not cause sickling.
Three splice site mutations are known to occur in exon 1 of the beta globin gene. These mutations result in three different abnormal haemoglobins: Malay, E, and Knossos. Haemoglobin E is a very common abnormal haemoglobin in Southeast Asia, as well as in India. The mutation GAG to AAG which leads to haemoglobin E, creates an alternate splice site competing with the normal splice site. This results in abnormal haemoglobin production and mild thalassaemia in the homozygous state, with a mild microcytic anaemia with a haemoglobin usually above 10 g%. Clinically, the affected persons are not ill, although a mild splenomegaly can develop. Electrophoresis reveals approximately 90% Hb E with varying amounts of Hb F.
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The heterozygote has a haemoglobin of about 12 g% with microcytosis and an electrophoretic pattern showing Hb E plus Hb A2 of 20 to 30%. On standard electrophoresis haemoglobin E co-migrates with Hb A2.
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When Hb E trait combines with a
b0 thalassaemia mutation, a severe transfusion-dependent (Eb0) anaemia will ensue. Eb 0 thalassemia patients who undergo splenectomy may stop being dependent on transfusions.
