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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Far East two types of alpha-thalassemia genes, namely alpha-thalassemia, (alpha-thal1), and alpha-thalassemia2 (alpha-thal2) exist. Definite diagnosis of the alpha-thal1 and alpha-thal2 traits is very difficult because their hematological findings are minimally abnormal or normal. This study attempts to characterize the heterozygotes by hemoglobin chain synthesis in reticulocytes from obligatory cases of the alpha-thal1 and alpha-thal2 traits. Twelve parents of babies with hemoglobin Bart's hydrops fetalis (obligatory alpha-thal1 trait) had the mean total radioactivity alpha/beta ratio of 0.76 +/- SD 0.04, while that of 7 normal controls was 1.06 +/- SD 0.04. The alpha/beta globin chain ratios of 16 cases, who were either parents or offspring of patients with hemoglobin H disease, were found to segregate into 2 groups, i.e. 0.78 +/- SD 0.03 (10 cases) and 0.9l1 and alpha-thal2 traits respectively. The hematological data of the first group showed definite hypochromic microcytic red cells, similar to those of the parents of the hydrops. The second group had significantly higher mean corpuscular hemoglobin than the first group, compatible with alpha-thal2 trait. Our globin chain synthesis study thus appears to be capable of discriminating normal, alpha-thal1 and alpha-thal2 traits.
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PMID:Haemoglobin synthesis in 28 obligatory cases for alpha-thalassemia traits. 117 33

Messenger RNA(mRNA) has been prepared from reticulocytes obtained from patients with different types of thalassaemia and assayed in the wheat germ system. Since normal human reticulocyte mRNA directs the synthesis of equal numbers of alpha- and beta-globin chains in this system it offers a rapid and simple technique for assaying mRNA in the thalassaemic disorders. In mRNA from beta+ thalassaemics the deficiency of beta-globin synthesis mirrored that observed in intact reticulocytes while that prepared from patients wiht haemoglobin H disease gave alpha/beta globin chain production ratios which showed consistently greater imbalance than was found in reticulocytes. Messenger RNA prepared from haemoglobin E-beta0 thalassaemics from Thailand directed no detectable beta-chain synthesis while that prepared from a betaO thalassaemic from Ferrara synthesized a fraction with the chromatographic characteristics of beta-globin chains.
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PMID:Assay of thalassaemic messenger RNA in the wheat germ system. 125 31

Globin chain synthesis was studied in the reticulocytes of 30 patients with various myelodysplastic syndromes (MDS) to determine the alpha:beta globin chain synthetic ratio and its probable prognostic value. The mean (SD) value of the total alpha:beta ratio was 0.82 (0.45) ranging from 0.05 to 1.73. The same ratio in 10 normal controls was 1.01 (0.04). This difference was significant. Furthermore, the alpha:beta ratios were lower than normal in 14 patients (alpha-thalassaemia-like) (group I), almost within normal limits in 11 (group II), and higher than normal in five (beta-thalassaemia-like) (group III). In each group almost all the FAB subtypes were represented. The addition of exogenous haem in several of the test samples resulted in a slight to pronounced increase in the alpha:beta ratios, particularly in group I. In 92% of the high risk cases (refractory anaemia with excess blasts (RAEB), chronic myelomonocytic leukaemia (CMML] or 87.5% of patients who finally developed acute non-lyphoid leukaemia (ANLL) low or normal alpha:beta ratios were found. No significant correlation was noticed between alpha:beta ratios and various haematological variables or survival. It is concluded that in MDS the alpha:beta ratio varied enormously across the entire population of patients, as well as within each FAB subtype, thereby restricting its prognostic value. Although haem deficiency may be implicated in some cases of MDS, why this should be remains unclear.
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PMID:Globin chain synthesis in myelodysplastic syndromes. 186 85

Red cell volume distribution curves were studied in alpha-thalassaemic mice (Hbath-J/+ mice) and normal mice (+/+ mice) of various ages. Individual Hbath-J/+ mice could not be reliably distinguished from their +/+ littermates on the basis of modal cell volume either at birth or during the first 3 weeks of life. However, between the ages of 4 and 30 weeks Hbath-J/+ mice displayed a degree of microcytosis that enabled them to be readily distinguished from their normal littermates using the criterion of modal red cell volume. Preliminary studies of alpha:beta globin chain synthesis ratios given by blood reticulocytes of Hbath-J/+ and +/+ mice after incubation with 3H-leucine for 5 min and 2 h suggest that there is little or no proteolysis of excess beta-chains in the alpha-thalassaemic mouse. Electron microscope studies revealed that the erythroblasts, marrow reticulocytes and circulating red cells of Hbath-J/+ but not +/+ mice contain stellate and branching intracytoplasmic inclusions, presumed to consist of precipitated beta-chains. These inclusions were ultrastructurally similar to the inclusions which have been previously reported in the erythroblasts and marrow reticulocytes of people with various alpha-thalassaemia syndromes. The proportion of erythropoietic cell profiles with inclusions was higher in Hbath-J/+ mice (in which two of the four alpha-globin genes are deleted) than in Thai patients with HbH disease (in whom there is usually a deletion of three of the four alpha-globin genes); this finding is probably related to a relatively low proteolytic capacity in the more mature mouse erythroid cells when compared with human cells. The presence of inclusion-containing red cells (mainly reticulocytes) in the peripheral blood of unsplenectomized Hbath-J/+ animals contrasts with the absence of such cells in unsplenectomized patients with alpha-thalassaemia I trait and HbH disease; this difference seems to be at least partly due to a poorly-developed pitting function in the mouse spleen.
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PMID:Red cell volume distribution curves and intracellular globin chain precipitation in the alpha-thalassaemic mouse, Hbath-J. 300 53

In this study, we analyzed the phenotypic manifestations resulting from the interaction of heterozygous beta zero-thalassemia(beta zero-39 nonsense mutation) with the functional loss of three alpha-globin structural genes in six subjects, of whom four had the [-alpha/--]alpha-globin genotype and two the [--/alpha Th alpha] alpha-globin genotype. The beta-thalassemia defect was in all cases the nonsense mutation at codon 39. The nondeletion alpha-thalassemia alpha th was the initiation codon mutation (AUG----GUG) of the alpha-2 gene. In all these subjects hypochromia and microcytosis were more marked than in beta zero-thalassemia heterozygotes with a full complement of four alpha-globin genes. All but one had moderate anemia. The alpha:beta globin chain synthesis ratios were consistently decreased. No cases had Hb H on electrophoresis. Subjects with [--/alpha Th alpha] alpha-globin genotype had more severe thalassemia-like manifestations than those with [--/-alpha] alpha-globin genotype.
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PMID:Interaction of heterozygous beta zero-thalassemia with single functional alpha-globin gene. 318 3

Hereditary spherocytosis and beta thalassaemia are rarely inherited together. We have studied a large family of Caucasian extraction in whom these two diseases segregate independently over four generations. The diagnosis rested on specialized laboratory findings and in a number of subjects on the measurement of alpha and beta globin chain synthesis. In addition, a viscometric method (osmotic gradient ektacytometry) was used to evaluate the rheological function of the erythrocytes. In patients inheriting both diseases, the results indicate that the clinical and biological expression of hereditary spherocytosis is modulated by the degree of imbalanced globin chain synthesis. The opposite properties of spherocytes (decreased surface/volume ratio, increased haemoglobin concentration) and thalassaemic red cells (increased surface/volume ratio, decreased haemoglobin concentration) may explain the antagonistic influence of each genotype.
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PMID:Occurrence of hereditary spherocytosis and beta thalassaemia in the same family: globin chain synthesis and visco diffractometric studies. 319 Oct 34

This paper describes a complex combination of four thalassemia genes (delta(+), beta(0), nondeletion and deletion alpha-thalassemia) in the spouse of a typical high Hb A2 beta-thalassemia carrier presenting for genetic counselling. This complex gene combination resulted in a hematological phenotype, characterized by thalassemia-like red cell indices, normal Hb A2 and Hb F levels and slightly reduced alpha/beta globin chain synthesis ratio, and therefore not indicative for the presence of beta-thalassemia trait. Family studies in combination with alpha-globin gene mapping, haplotype analysis at the beta-globin gene cluster and definition of the beta-thalassemia mutation by oligonucleotide hybridization led us to identify a beta-thalassemia mutation, to define the molecular basis for this phenotype and give the appropriate genetic counselling.
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PMID:Pitfalls in genetic counselling for beta-thalassemia: an individual with 4 different thalassemia mutations. 335 76

Ferrokinetic studies, alpha globin gene mapping, and assessment of iron status have been carried out in 16 healthy subjects with heterozygous beta thalassaemia. Six subjects had coinherited alpha thalassaemia and had more balanced alpha/beta globin chain synthesis ratios than the remaining 10 subjects with uncomplicated heterozygous beta thalassaemia. The overall efficiency of erythropoiesis was significantly reduced in the latter group (mean 76 +/- 17 (SD)% of normal), but was indistinguishable from normal in subjects with coexistent alpha thalassaemia. Red cell survival was unimpaired in both groups, indicating that the defect was one of mild ineffective erythropoiesis rather than peripheral haemolysis. Values for total plasma iron turnover were normal or only slightly increased. This suggests a lack of any additional stimulus to erythropoiesis, which might normally be expected to compensate easily for the mild degree of anaemia. Uncomplicated heterozygous beta thalassaemia produces an extremely mild disorder of erythropoiesis, which is dependent on the imbalance between alpha and beta globin chain synthesis, and is not associated with a risk of serious iron overload.
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PMID:Erythrokinetics and iron status in heterozygous beta thalassaemia, and the effect of interaction with alpha thalassaemia. 359 48

The gene frequencies of abnormal haemoglobins have been determined in a group of 100,000 Jamaican newborns screened over a period of 8 1/2 years. The population is predominantly of West African origin and the survey represents approximately one quarter of all island deliveries within the period of the study. The common beta globin chain abnormalities beta s and beta c occurred with gene frequencies of 0.055 and 0.019 respectively; beta thalassaemia was relatively rare. In contrast, alpha thalassaemia was quite common, occurring with a gene frequency of 0.183. In addition to these common abnormalities, the frequencies of 256 rare abnormal haemoglobins are described. This survey thus represents a complete and accurate documentation of the alpha and beta globin variants that occur in the Jamaican population.
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PMID:Haemoglobin gene frequencies in the Jamaican population: a study in 100,000 newborns. 377 23

Six Algerian patients with beta 0 thalassemia are presented, in addition to the two patients already reported (Godet et al., 1977). Family studies indicate that all the patients had homozygous beta thalassemia characterized by absence of beta globin chain synthesis in peripheral blood. The clinical severity varies from one family to the other and within the same family, from typical Cooley's anemia to thalassemia intermedia and appears to be related to the child death rate observed in each family. The gamma/alpha biosynthetic ratio was 0.36-0.40 in seven patients and 0.2 in the most seriously affected patient. The mRNA beta content in peripheral reticulocytes was less than 1.5% of mRNA alpha in seven patients and 13.3% in one patient. These results indicate that Algerians homozygous for beta 0 thalassemia are heterozygous at the clinical, biochemical and molecular levels.
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PMID:Heterogeneity in beta 0 thalassemia from Algeria: genetic, clinical and molecular studies. 615 18


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