Hemoglobin Syracuse (alpha2beta2-143(H21)His leads to Pro), a new high-affinity variant detected by special electrophoretic methods. Observations on the auto-oxidation of normal and variant hemoglobins.

Abstract

Family members from four generations were found to have polycythemia and increased whole blood 02 affinity (P50; 11 mm Hg; normal, 27 mm Hg). No abnormal hemoglobin bands were seen after electrophoresis on starch gel at pH 8.6 or agar gel at pH 6.0. Analysis of the oxygenated hemolysate by isoelectric focusing on polyacrylamide gel revealed two closely spaced bands. When deoxygenated hemolysate was analyzed in oxygen-free gels, the two components were more widely separated. About 40% of the patient's hemoglobin focused at a more acid pH than hemoglobin A, indicating a hemoglobin variant with impaired Bohr effect. Chromatography of globin in 8 M urea revealed two p-chain peaks, the first of which was eluted at a lower buffer molarity than normal # chain. Fingerprints of tryptic digests of the aminoethylated chains were done on silica gel thin-layer plates. Tp 14 from the abnormal # chain had slower electrophoretic mobility and a greater R. value. Amino acid analyses of this peptide gave values identical with those of j#Tp 14, except that it contained one proline residue and no histidine. Since the one His in #Tp 14 is in position 143, hemoglobin Syracuse is a2PlBHis'PrO. Native Hb Syracuse could be separated from hemoglobin A on a carboxymethylcellulose column. The inclusion of 0.1 mM EDTA in the preparaDr. Jensen was a fellow of the Deutsche Forschungsgemeinshaft.

Haemoglobinopathies with high oxygen affinity. Experience of Erythropathology Cooperative Spanish Group

“…Mutations experienced by amino acids enclosed in these zones, which are critical for haemoglobin functions, can therefore determine alterations in affinity to oxygen [11]. Of the ten high-affinity haemoglobinopathies found by our laboratory, in four (Hb San Diego, Hb Johnstown, Hb Malmö and Hb Columbia-Missouri), the amino acid change affects the α 1 β 2 contact zones [12][13][14][15], while in two (Hb Strasbourg and Hb Syracuse) the bonds to 2,3-DPG, in the central cavity, are affected [16,17], and in another two (Hb Badalona and Hb La Coruña) the contact cavity to the haem group [18,19] is affected and in one (Hb Bethesda) the α 1 β 1 contact zone is affected [20]. But, in the Hb Olympia, the amino acid change is located in site 20 of the chain helix B and there is no relation to any of the aforementioned zones, but it is accompanied by erythrocytosis.…”

Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.

“…The white cell and platelet counts are often normal, but in many cases these data were not recorded. Nevertheless, a raised white count was found in at least four families from the 16 variants so far reported: in association with Hb Ypsilanti2l (1 out of 14 (14 g/dl), though the red cell count was raised (7 5 x 1012/1 (7 500 000/mm3) ) with hypochromic erythrocytes. This case was complicated, however, by the possible presence of p-thalassaemia, which may have prevented the development of a high haemoglobin concentration.…”

Secondary Erythrocytosis Due to Compound Homozygosity, but not Compound Heterozygosity, for Hb Luton and α-Thalassemia: A Family Study

“…However, there were a small minority that had symptoms presumed to be secondary to the erythrocytosis. The symptoms described were as follows, in order of frequency: headaches (17)(18)(19)(20)(21); dizziness (19,20,(22)(23)(24); easy fatigability (17,22,25,26); tiredness (23,26,27); chest pain (17,22,23); weakness (18); intermittent claudication (28); symptoms of hyperviscosity (29); peripheral cyanosis (23), and epistaxis (18). In those who were symptomatic, most had a trial of venesection for symptomatic relief and this was sometimes associated with an improvement in symptoms.…”