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A recently initiated collaboration between Russian and American institutions has resulted in the characterization of several known or new beta-thalassemia alleles and unstable hemoglobin types. Nine known beta-thalassemia alleles were present which have also been found in Mediterranean, East Asian, and Black populations; the possibility of independent mutations for some of the rare alleles should be considered. Hb Durham-N.C./Brescia with a codon 114 (CTG-->CCG; Leu-->Pro) change was present in six members of two families. This condition and two new variants have the characteristics of a dominant type of beta-thalassemia heterozygosity with moderate anemia, Heinz body formation, splenomegaly, etc. One new beta-thalassemia allele is a frame-shift at codon 124 (-A), while another is characterized by the introduction of an extra proline residue (codon: CCA) between residues Thr (beta 123) and Val (beta 126) to give the sequence -Thr-Pro-Pro-Pro-Val-.

We have identified a valine-->methionine mutation at position 67 of the beta chain in the hemoglobin of a young Russian patient with severe hemolytic disease, anemia, splenomegaly, Heinz body formation, and continued requirement for blood transfusions despite an early splenectomy. Sequencing of amplified DNA readily identified a GTG-->ATG mutation at codon 67. The introduction of the larger methionine residue into the heme pocket, and the loss of the bonds between valine at beta 67 and the heme group, adequately account for the severe instability of Hb Alesha and the serious clinical condition of its carrier.

Iron metabolism was studied in 10 patients with malignant histiocytosis (MH), in 16 patients with histiocytosis-X (Langerhans cell histiocytosis) and in 34 patients with reactive proliferation of the mononuclear phagocytes (MPS). Eight MH patients had a considerably increased level of serum ferritin (SF). The average level of SF was 6070 +/- 957 mg/l for MH patients, which is significantly greater than the SF level for HX and RH patients. The study of the serum ferritin profiles suggests that the main pathogenetic mechanism of hyperferritinaemia in MH is the synthesis and secretion of ferritin by neoplastic mononuclear phagocytes. From this, hyperferritinaemia in MH may be considered as pathognomic of this disease and used as an additional diagnostic criterion. In addition, SF is the most informative parameter for the clinical practice among the indices of the functional state of MPS.

The erythrocyte membrane protein of band 4.1 is an essential protein of the erythrocyte cytoskeleton. Two isoforms have been detected in human erythrocytes, and six in nucleated avian erythrocytes. Multiple alternative splicing of human reticulocyte mRNA for protein 4.1 implies the possibility of even more isoforms. Structural and functional dissimilarities between isoforms, and their differential expression during the course of erythropoiesis are not well understood. Here, we show that only protein 4.1b is present in the immature reticulocytes of anaemic patients. The ratio of 4.1a to 4.1b in mature reticulocytes of healthy individuals was 1.25. This ratio was 2.0 in healty mature erythrocytes, and 0.7 in peripheral red blood cells from anaemic patients. Taking into account these and other available data, we speculate that the steady state levels of protein 4.1 isoforms change gradually in the terminal stages of erythropoiesis.

An electrophoretically I-like hemoglobin variant was detected during a survey for abnormal hemoglobins in Dagestan (USSR). Neither clinical nor hematological abnormalities were seen in the carrier for this mutant hemoglobin. Structural studies demonstrated a previously undescribed substitution of alpha 60 (E9) Lys leads to Glu.