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)

25-yr old female identical twins of Italian-American origin concordant for sickle beta-thalassemia were studied to explain their clinical differences. One of them has been severely affected from childhood with one aplastic crisis, an earlier onset of vaso-occlusive crises, and recent cardiac decompensation; the other twin shows no cardiac decompensation. Similar are their degree of anemia, RBC indices, blood volumes, absence of splenic sequestration, depression of pO2, elevation of p50 and 2,3-DPG, hemoglobin composition, and peripheral blood globin-synthetic rates. Regarding differences, the more severely affected has a shorter 51Cr RBC life span, a greater menstrual blood loss, and is more overweight, whereas the less severely affected has functional asplenia by 99mTc scanning and a larger proportion of RBC with decreased cellular deformability. We conclude that in sickle beta-thalassemia: (1) genotype alone does not determine the clinical course; (2) significant differences in clinical course can occur with almost identical hemoglobin composition and globin synthetic rates; (3) cellular deformability changes do not correlate exactly with clinical course; and (4) functional asplenia and leanness may be advantageous.
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PMID:Sickle beta-thalassemia: identical twins differing in severity implicate nongenetic factors influencing course. 98 45

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

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.
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PMID:Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias. 123 8

Hematologic and globin synthesis studies were performed in a black American family in which the genes for alpha-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait + alpha-thalassemia; mother, HbC trait + alpha-thalassemia, propositus, HbSC + alpha-thalassemia; older sibling, alpha-thalassemia trait; and younger sibling, hemoglobin H disease. The child with HbSC-alpha-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2, 3-diphosphoglycerate (2, 3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin H disease exhibited 26% Bart's (gamma4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin H disease appeared, with HbH making up 6.5% of the total hemoglobin.
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PMID:Sickle cell syndromes. I. Hemoglobin SC-alpha-thalassemia. 127 38

Recent studies from this department have suggested that the level of 2,3-DPG may be determined in part by the volume of the erythrocyte; this conclusion was reached on the basis of the finding of significantly elevated values of 2,3-DPG in heterozygous beta-thalassemia, even in the absence of anemia. In order to test the role of microcytosis in the formation of 2,3-DPG levels, a study was undertaken on a different patient material characterized by microcytosis without anemia or hypoxia, namely on cases of polycythemia vera (PV) rendered microcytic through therapeutic venesection (or blood loss) and on appropriate controls. Five cases of untreated PV (mean HB 18.36 +/- 1.53 g/dl, mean MCV 94.4 +/- 3.9 fl) had 2,3-DPG levels slightly lower than normal controls (13.67 +/- 0,75 mumoles/g Hb vs 14.18 +/- 1.41 mumoles/g Hb). Six microcytic iron deficient PV's (mean Hb 17.42 +/- 2.34 g/dl, mean MCV 74.5 +/- 6.2 fl) had very significantly increased 2,3-DPG levels (17.73 +/- 1.75 mumoles/g Hb). Similar high levels were obtained in five cases venesected in the past and maintained with cytostasis (mean Hb 15.22 +/- 0.67 g/dl, MCV 82.5 +/- 7.5 fl, 2,3-DPG 17.04 +/- 2.44 mumoles/g Hb). A strong linear negative correlation was obtained between 2,3-DPG values and the MCV (r = -0.736, P less than 0.001). It is concluded that microcytosis of other etiology and not only of beta-thalassemia may also lead, per se, to increased levels of 2,3-DPG. The different levels of 2,3-DPG in PV undergoing venesection vs untreated patients may explain some discrepant reports on the behavior of this metabolite in PV.
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PMID:[Erythrocyte volume and 2,3-DPG level. A study on a primary polycythemia model]. 662 51

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

The chemical and physical properties of haemoglobin S derived from homozygotes for this haemoglobin in Sicily were examined, as well as some erythrocytic characteristics. Sicilian Hb S was identical to that found in USA black patients in electrophoretic mobility on both starch and citrate agar media, solubility, mechanical precipitation rate of oxyhaemoglobins, and minimum gelling concentration, as well as by peptide mapping and amino-acid analysis of all beta-chain peptides. Taken together with the presence in Sicily of African blood group markers and certain historical considerations, it seems clear that the source of Hb S in Sicily is Africa. While the clinical severity in nine Sicilian children did not seem remarkably different from the disease in the USA, the most severe and fatal complications were not seen. Mean Hb F Was 10.5% and 2,3-diphosphoglycerate (2,3-DPG) values were higher in Sicilian homozygotes than in black USA counterparts (21.79 mumol/g Hb vs 15.16). Red cell AT values were also slightly higher in Sicilian patients. The presence of concomitant thalassaemia was excluded by both family studies and globin chain synthetic ratios. In conclusion, haemoglobin S in Sicilian homozygotes is identical to Hb S found in USA blacks. Although the severity of the disease seems quite similar in both groups of patients, other erythrocytic properties were found to be different. Whether these factors influence severity remains to be elucidated.
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PMID:Sickle cell disease in Sicily. 736 60

Phosphorus-31 nuclear magnetic resonance (NMR) spectra were determined from intact erythrocytes of a patient with homozygous beta-thalassemia and from three patients with pyruvate kinase (PK) deficiency. The intracellular 2,3-diphosphoglycerate-(2,3-DPG) were mildly elevated in the thalassemia patient and in PK heterozygotes, and were markedly elevated in the PK-deficient homozygotes. The 2,3-DPG chemical shifts in the patients' NMR spectra were consistently positioned at a higher magnetic field than normal. When the patients with thalassemia or PK deficiency were transfused with blood from a normal donor, or when a patient's erythrocytes were mixed with normal erythrocytes, two distinct sets of 2,3-DPG resonances appeared in the resulting spectra, allowing the simultaneous quantification of the 2,3-DPG levels in each erythrocyte population. The ability of NMR to detect heterogeneous cell populations may be useful for the diagnosis of congenital hemolytic anemias in patients who have been transfused.
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PMID:31P NMR spectroscopy of erythrocytes in congenital hemolytic anemias: detection of heterogeneous erythrocyte populations and quantification of intracellular 2,3-diphosphoglycerate. 743 1

13C and 31P magnetic resonance spectroscopy was used to characterize the in vivo kinetics of glucose metabolism and intracellular ATP and 2,3-DPG concentrations in erythrocytes obtained from beta-thalassaemia intermedia, heterozygous beta-thalassaemic and normal individuals and maintained in suspension. Except for an upfield chemical shift in the 2P and 3P resonance of 2,3-DPG in the thalassaemia intermedia erythrocytes, the 31P spectra were comparable between all three blood types, showing similar concentrations of ATP (from 4.5 to 5.2 mumol/g Hb) and 2,3-DPG (from 17.2 to 19.7 mumol/g Hb). However, the profile of glucose metabolism was quite different in beta-thalassaemia intermedia erythrocytes, whereas glucose was consumed at a rate of 0.089 +/- 0.035 fmol/cell/h, significantly higher than that of normal (0.032 +/- 0.018 fmol/cell/h; P = 0.01) and heterozygous (0.025 +/- 0.004 fmol/cell/h; P = 0.01) erythrocytes. This near 3-fold faster rate of glucose metabolism in the thalassaemia intermedia erythrocytes could not be accounted for by any increase in glucose flux via the Embden-Meyerhof pathway, since no significant difference in 3-13C-lactate synthesis was observed among the three blood types (in units of fmol/cell/h, normal, 0.021 +/- 0.013; heterozygous, 0.021 +/- 0.006; beta-thalassaemia intermedia 0.045 +/- 0.025). These results reflect an accelerated rate of glucose metabolism in thalassaemia intermedia erythrocytes because the contribution of reticulocytes to this altered pattern of metabolism could be excluded. As the only other route of glucose metabolism in erythrocytes is the pentose phosphate pathway (PPP), these results indicate that the PPP is more active in beta-thalassaemia intermedia erythrocytes, perhaps as a consequence of their elevated intracellular oxidative state.
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PMID:In vivo metabolic studies of glucose, ATP and 2,3-DPG in beta-thalassaemia intermedia, heterozygous beta-thalassaemic and normal erythrocytes: 13C and 31P MRS studies. 781 67

The primary pathophysiological event in the erythrocytes of individuals with the various sickle syndromes is the intracellular aggregation or polymerization of sickle haemoglobin (HbS). The extent of polymerization is determined by the intracellular haemoglobin composition (% HbS and % HbS A, A2 and F), concentration (MCHC and % of dense cells) and oxygen saturation, as well as minor factors such as intracellular pH and DPG concentration. Intracellular HbS polymerization leads to a marked decrease in the flexibility or rheological properties of the sickle erythrocytes and obstruction in various microcirculatory beds, as well as chronic anaemia. Other abnormalities in the properties of the sickle erythrocytes, including membrane abnormalities, changes in ion fluxes and volume and endothelial adhesion, result from acute and chronic oxygen-linked polymerization events and may, in turn, modify polymerization. However, within a good approximation, many aspects of sickle cell disease pathophysiology--for example variations in anaemia among the different sickle syndromes--can be explained in terms of differences in polymerization tendency. Thus, the effects of alpha-thalassaemia can be explained with reference to changes in MCHC and syndromes with high HbF are understandable in terms of the sparing effect of HbF on polymerization. Recent therapeutic approaches to sickle cell disease focus on attempts to reduce intracellular HbS polymerization by altering the haemoglobin molecules, erythrocyte properties, or the distribution of intracellular haemoglobin species. The last, through pharmacological elevation of HbF, has become the central focus of much laboratory and clinical research in recent years. Agents such as hydroxyurea (with or without recombinant erythropoietin) and butyrate compounds elevate HbF (and reduce HbS) in a majority of sickle erythrocytes, thus decreasing intracellular polymerization. Current prospective protocols are designed to see if these changes cause clinical improvement at acceptable doses. Other treatment strategies, including bone marrow transplantation and possible gene replacement therapies, are also under active clinical or laboratory investigation.
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PMID:Sickle cell disease pathophysiology. 835 18


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