1/11. Hb Cardarelli [beta86(F2)Ala-->Pro]: a new unstable and hyperaffine variant in association with beta( )-thalassemia.Hb Cardarelli [beta86(F2)Ala-->Pro] is a new unstable and high oxygen affinity variant found in several members of a family from Naples, Southern italy. A detailed structural and functional characterization of the variant was performed on two subjects, at both the protein and dna level. The first patient exhibited 43% of the variant hemoglobin (Hb) without major hematological problems. The proband showed 82% of the abnormal Hb in association with beta( )-thalassemia (thal) that caused relevant erythrocytosis requiring frequent phlebotomies. Structural investigation of the Hb variant by mass spectrometric methodologies identified the amino acid replacement as Ala-->Pro at beta86. The corresponding dna mutation GCC-->CCC at codon 86 of the beta-globin gene was assessed by both dna sequencing and amplification refractory mutation system (ARMS) techniques. Functional studies carried out on whole blood and diluted hemolysates from both patients demonstrated increased oxygen affinity, decreased Bohr effect, reduced heme-heme interaction and nearly halved 2,3-diphosphoglycerate (2,3-DPG) and chloride effects.- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
2/11. Hb Johnstown [beta109(G11)Val-->Leu]: A high oxygen affinity variant associated with beta0-thalassemia.Hb Johnstown [beta109(G11)Val-->Leu], a high oxygen affinity hemoglobin (Hb) variant associated with beta0-thalassemia (thal) [IVS-I-1 (G-->A)], was identified in an 8-year-old girl referred to our laboratory because of erythrocytosis and a left-shifted oxygen dissociation curve (ODC). The phylogenetic tree showed that the mother was heterozygous for the Hb variant and the father was a beta0-thal carrier. This Hb variant, with normal electrophoresis, was characterized at the dna level by beta gene sequencing. The amino acid substitution potentially disrupts alpha1beta1 contacts i n the deoxyHb conformation, thus shifting the equilibrium towards the high affinity oxyHb conformation. The erythrocytosis and low values for actual P50 due to Hb Johnstown were more marked due to the co-inheritance of the beta0-thal.- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
3/11. A new highly unstable alpha chain variant causing alpha( )-thalassemia: Hb Zurich Albisrieden [alpha59(E8)Gly-->Arg (alpha2)].A new alpha-globin mutation causing persistent mild hypochromic microcytosis and erythrocytosis is described. Hb Zurich Albisrieden [alpha59(E8)Gly-->Arg (alpha2)] is not detected at the protein level and leads to alpha( )-thalassemia (thal).- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
4/11. Hb zoeterwoude [beta23(B5)Val-->Ala)]: a new beta-globin variant found in association with erythrocytosis.We describe the characterization of a new hemoglobin (Hb) variant found in a 77-year-old Dutch woman, suspected of hypoxia-mediated erythrocytosis. The typical blood parameters (Hb 17.3 g/dL; PCV 0.525 L/L; RBC 5.82 x 10(12)/L) could not be explained by any of the pathological or physiological conditions causing erythrocytosis. The patient was preventively phlebotomized because of intermittent claudication and erythrocytosis. At the hematological and biochemical levels, no anemia or hemolysis were present and no abnormal Hb fractions were detectable on alkaline electrophoresis or high performance liquid chromatography (HPLC). Molecular analysis revealed intact alpha-globin genes and a heterozygosity for a GTT-->GCT transition at codon 23 of the beta-globin gene, causing a Val-->Ala amino acid substitution. The P50 measured in full blood indicated that this mutant has an elevated oxygen affinity. This is the fourth single nucleotide substitution at codon 23 of the beta gene and the second associated with erythrocytosis. Because the family was not available for investigation no information was obtained as to whether the mutation represents a de novo event or was inherited, and might be a more common cause of erythrocytosis in Dutch patients. Considering the relatively high frequency of beta-thalassemia (thal) in the large allochthonous population in The netherlands, combinations of Hb Zoeterwoude and beta-thal traits may lead to hemizygosity, with severe hypoxia and erythrocytosis from a few months after birth.- - - - - - - - - - ranking = 0.2keywords = thalassemia (Clic here for more details about this article) |
5/11. The homozygous state for Hb Crete [beta129 (H7) Ala-->Pro] is associated with a complex phenotype including erythrocytosis and functional anemia.Hb Crete, an electrophoretically neutral, unstable, high oxygen affinity variant, was characterized by protein and dna analyses in the homozygous state in a 32-year-old woman from Crete, with erythrocytosis and microcytosis. The proband and members of her family over 3 generations, including 5 carriers of Hb Crete, were subject to clinical, hematological and biochemical investigations, and dna, rna and protein studies were carried out. The proband demonstrated features associated with disturbed hemoglobin (Hb) structure and function, including erythrocytosis and additionally a state of functional anemia, the latter reflected by increased erythropoetin levels and cardiac output. In addition, all the carriers surprisingly had hematological and biosynthetic findings more usually associated with thalassemia trait. The structural change in Hb Crete only partly explains all the pathological manifestations of this variant, and other mechanisms are discussed.- - - - - - - - - - ranking = 0.2keywords = thalassemia (Clic here for more details about this article) |
6/11. Homozygous hemoglobin Abruzzo in a North American child.Hemoglobin Abruzzo is a stable hemoglobin variant with increased oxygen affinity, clinically causing compensatory erythrocytosis in affected patients. Heterozygosity of this variant with or without beta-thalassemia has been previously described in three Italian families, thereby suggesting a single origin of the mutation. The authors report the first case of homozygosity in a North American female infant, born to heterozygous parents as a product of consanguineous marriage.- - - - - - - - - - ranking = 0.2keywords = thalassemia (Clic here for more details about this article) |
7/11. Double heterozygosity for hemoglobin Malmo [beta 97 (FG 4) HisGln] and beta-thalassemia traits. A 32-year-old Sicilian man had marked erythrocytosis (Hb = 23.0 g/dl, RBC = 10.5 x 10(12)/l, MCV = 71 fl, Hct = 84-92%, a 4.5 times increase in total erythropoies) and saphenous system varices, without other clinical abnormalities. By Hb electrophoresis, an abnormal Hb migrating slightly more anodally than Hb A was found. HbA0 was almost completely absent. The abnormal Hb was recognized to be Hb Malmo [beta 97 (FG4) His-Gln], a human Hb variant with greatly increased oxygen affinity. The patient was also a carrier of the beta-thalassemia trait. The father of the propositus was a heterozygous carrier of Hb Malmo (about 40% of total Hb), while his mother had only a beta-thalassemia condition. This is the first reported case of double heterozygosity for both Hb Malmo and beta-thalassemia, thus producing complete absence of normal Hb.- - - - - - - - - - ranking = 1.4keywords = thalassemia (Clic here for more details about this article) |
8/11. Hemoglobin San Diego/beta zero thalassemia in a Greek adult.Interaction of beta zero thalassemia with Hb San Diego [a high affinity hemoglobin variant, alpha 2 beta (2)109(G11)Val Met] in a 29-year-old Greek male is described. A marked polycythemia with low MCH and MCV, but minor clinical problems were observed. Functional properties of the isolated variant are described.- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
9/11. Sickle cell thalassemia, thrombocytosis, and erythrocytosis.A patient with sickle cell beta -thalassemia had thrombocytosis and erythrocytosis due to a myeloproliferative disorder best classified as polycythemia vera. RBC counts were 6 to 8 million/cu mm and the red cell mass was 33 ml/kg. A higher red cell mass and an increased hematocrit value were prevented probably by factors related to the hemoglobinopathy, such as microcytosis and hemolysis. The diagnosis of polycythemia vera in patients with sickle cell disease may be difficult to document and the association of these disorders has not been previously reported. This patient's high red blood cell and platelet counts did not result in recurrent vasoocclusive crises.- - - - - - - - - - ranking = 1keywords = thalassemia (Clic here for more details about this article) |
10/11. Regulation of erythropoietin production in a case of congenital erythropoietin-dependent pure erythrocytosis.In a patient with congenital erythropoietin-dependent pure erythrocytosis (EDPE) associated with hypersensitivity of erythroid progenitor cells to erythropoietin (Epo), the investigations planned to elucidate the mechanism responsible for hormone hyperproduction revealed that Epo synthesis was (1) independent of normal oxygen-mediated feedback induced by phlebotomy; (2) not modulated by adenosine as a second messenger (the treatment with the adenosine antagonist theophylline in fact left unchanged the serum Epo levels); and (3) uninfluenced by iron therapy. The Epo dose-response curve for growth of erythroid progenitor was similar to that of three age-matched thalassemia patients with increased serum Epo levels, (sEpo) suggesting that the observed erythroid progenitors hypersensitivity to Epo could represent an ex vivo artifact induced by the increased sEpo levels.- - - - - - - - - - ranking = 0.2keywords = thalassemia (Clic here for more details about this article) |
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