Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because their blood may "unload" oxygen more readily than normal, people with hemoglobin of low oxygen affinity might be expected to be anemic. We have studied a woman with hemoglobin Hope/beta+ thalassemia, whose hemoglobin level was 10.4 to 12.3 gm/dl (normal 14 +/- 2) despite a P50 of 41 mm Hg (normal 26). Her cardiac index was normal, yielding a calculated mixed venous PO2 of 51 mm Hg (normal 34 to 49). Oxygen transport in patients with low oxygen affinity can be maintained by a variety of homeostatic responses, only one of which is altered erythropoiesis.
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PMID:Oxygen transport in a woman with hemoglobin Hope/beta+ thalassemia. 42 43

Oxygen dissociation studies were carried out on haemoglobin E (Hb E) at both high and low haemoglobin concentrations. Oxygen affinities of fresh red cells from three people homozygous for Hb E and from one with Hb E-beta thalassaemia (Hb-E trait/beta-thal trait) were low in three out of four patients studied, while the oxygen affinity of red cells from an individual with Hb-E was normal 2,3-DPG concentration in the fresh cells from the people with homozygous Hb E or Hb-E trait/beta-thal trait which showed low oxygen affinities were elevated sufficiently to account for the shifts observed. When the cells from two of these people with homozygous Hb E were depleted of 2,3-DPG. their oxygen affinities became the same as that of similarly treated normal cells. Pure 'stripped' Hb E in dilute solution behaved identically to Hb A in respect of P50, Bohr shift, haem-haem interaction, and interaction with inorganic phosphate or 2,3-DPG. Hb E, therefore, has the same oxypgen dissociation properties as Hb A both in dilute solution and in the red cell. The low oxygen affinities found in the fresh cells and in whole blood are caused by high 2,3-DPG concentrations within the cell.
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PMID:The oxygen affinity of haemoglobin E. 120 Dec 9

Hb Geelong [beta 139(H17)Asn----Asp] was detected in a German woman of Polish-Russian descent. It is an unstable variant which appears to increase the severity of a beta (+)-thalassemic phenotype in the propositus. The electrophoretic properties of Hb A and Hb Geelong are similar on cellulose acetate in both acidic and alkaline conditioning. The electrophoretic mobility and the amino acid analysis of beta XT-14 indicated the substitution Asn----Asp at beta 139. The sequence of beta XT-14 was confirmed by dansyl-Edman degradation. The slight increase observed in the P50 of whole blood is not intrinsic to the beta 139 substitution, but is thought to result from an increased 2,3-diphosphoglycerate level in response to anemia. No family studies were possible to investigate the mode of inheritance of either beta (+)-thalassemia or Hb Geelong in the propositus. Synthetic globin chain ratios suggest that impaired synthesis of the variant globin chain is partially responsible for the low level of Hb Geelong in peripheral blood.
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PMID:Hb Geelong [beta 139(H17)Asn----Asp]. 191 39

Hb Knossos (beta 27 (B9) Ala----Ser) is a recently discovered hemoglobin variant endowed with beta-thalassemic properties (1,2) We present the first homozygous cases. The propositus, a 19-year-old man is originally from northeast Algeria, but is unrelated to other Algerians who have hemoglobin Knossos. He has a beta(+)-thalassemia intermedia syndrome, including microcytic, hypochromic anemia, enlargement of the spleen, and an increase in the number of reticulocytes. The reduction of beta-chain synthesis is pronounced (alpha/non alpha:2.76). Whole cells containing Hb Knossos have a dramatically low oxygen affinity (P50:38 mm Hg). The propositus also has homozygous delta(0)-thalassemia. The chromosome carrying these mutations is characterized by the DNA haplotype I.
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PMID:Homozygous hemoglobin Knossos (alpha 2 beta 227(B9) Ala----Ser): a new variety of beta (+)-thalassemia intermedia associated with delta (0)-thalassemia. 395 38

We report on a 54 years-old male patient from North-Eastern Algeria who combines two hemoglobin variants that are associated with thalassemia-like disorders: Hb Lepore and Knossos (beta 27 Ala----Ser) (1, 2). A beta-thalassemia intermedia picture gradually developed and finally required splenectomy at the age of 53. Total absence of Hb A2 indicated that the beta Knossos gene is most probably flanked with a delta(0)-thalassemia gene. No DNA deletion additional to the Lepore deletion was found. Hb F was elevated (12.3%) with 24% G gamma Hb F. In whole cells, Hb Knossos, representing 70% of total hemoglobin, displayed a decreased affinity for oxygen (P50 = 35 mm Hg), a fact presumably accounting for the relatively good tolerance of the condition.
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PMID:The association of hemoglobin Knossos and hemoglobin Lepore in an Algerian patient. 646 99

The levels of 2,3-DPG and the value of P50 were determined in unselected, clinically healthy, typical beta-thalassemia heterozygotes and normal controls. Values of 2,3-DPG in the heterozygotes are significantly elevated compared to normals (when expressed per gram of hemoglobin or per volume of red cells) and much higher than their mild hemoglobin deficit would explain; they are elevated even in selected heterozygotes presenting normal hemoglobins levels. These 2,3-DPG values, when expressed per number of erythrocytes, are within normal limits. In parallel, oxygen affinity is lower, as the P50 value is displaced to the right by 2 mmHg above the normal mean, thus assuring adequate tissue oxygenation. The findings suggest that the high 2,3-DPG values of the beta-thalassemia heterozygotes are not determined solely by anemic hypoxia; it is more likely that the microcytic erythrocytosis of heterozygous beta-thalassemia is the cause of this increase. The resulting lower oxygen affinity leads to a decreased stimulation of erythropoiesis and hence to its regulation at lower hemoglobin levels. Accordingly we suggest that the beta-thalassemia trait is a pseudo-anemia, because it is unlikely that these heterozygotes are unable to reach normal hemoglobin values by increasing erythrocyte output.
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PMID:[Anemia 2,3-DPG and tissue oxygenation in beta-thalassemia heterozygotes]. 716 85

High total haemoglobin levels in homozygous sickle cell (SS) disease are a risk factor for painful crises, avascular necrosis of the femoral head, proliferative sickle retinopathy, and the acute chest syndrome. Since lowering the haemoglobin level may ameliorate these features, understanding the determinants of total haemoglobin may be of practical importance. A range of possible determinants including red cell characteristics, reticulocytes, serum iron, transferrin saturation, serum ferritin, alpha thalassaemia status, red cell mass and plasma volume, oxygen affinity, red cell survival, transferrin receptor and erythropoietin levels have been measured in 62 patients selected to provide a range of total haemoglobin and fetal haemoglobin levels. There were weak negative associations of haemoglobin with mean cell volume and mean cell haemoglobin concentration, strong negative associations with proportional reticulocyte counts, oxygen affinity, plasma volume, serum transferrin receptors, and erythropoietin levels and strong positive associations with red cell mass. Weighted analysis suggested that the statistically independent determinants of haemoglobin level were alpha thalassaemia, sex, red cell mass/body weight, plasma volume/body weight, fetal haemoglobin, and red cell count. The apparent contributions of red cell survival, P50, reticulocyte count, serum transferrin receptor and erythropoietin levels were explained by the effects of these other variables. The independent determinants as a group explained 91% of the variation in haemoglobin level.
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PMID:Determinants of haemoglobin level in steady-state homozygous sickle cell disease. 856 87

Since the obtained results from the pilot study indicated that dilazep which was a membrane stabilizer would be benefit to treatment and prevention of anemia and chronic leg ulcer in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients, the authors had continued the study in a second phase, ie a double blind placebo control trial. Twenty-seven beta-thal/HbE patients were recruited in the study. Eight patients who suffered from chronic leg ulcer were given dilazep. The rest of patients were given dilazep or placebo according to a randomized table. Hence, 16 patients received dilazep and 11 received placebo. When we compared the number of unit of blood transfusion, hemoglobin level, 2-3 DPG and P50 value between the dilazep and placebo groups using unpaired t-test, we found that there were no statistical differences in any of the parameters. However, when we compared the data within the group using paired t-test, there was statistical decrease in blood requirement after treatment in the dilazep group (p < 0.05). Concerning with the treatment of chronic leg ulcer, 3 in 8 patients were completely healed within 3 months, 4 in 8 patients were improved and 1 in 8 patients was not improved. There were complaints of skin itching and mild epigastric pain in placebo group but the liver function tests, kidney function tests and cardiac enzyme did not significantly change during the medication.
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PMID:A double-blind placebo control trial of dilazep in beta-thalassemia/hemoglobin E patients. 964 Jun 22

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.
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PMID:Hb Johnstown [beta109(G11)Val-->Leu]: A high oxygen affinity variant associated with beta0-thalassemia. 1565 89

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.
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PMID:Hb zoeterwoude [beta23(B5)Val-->Ala)]: a new beta-globin variant found in association with erythrocytosis. 1576 51


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