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)

Minor fetal hemoglobins in red cell hemolysates of newborn and adults with elevated levels of Hb F have been separated and quantitated by Biorex 70 column chromatography. In addition to Hb F1, other minor hemoglobin zones eluting before F1, pre-F1, and after F1, post-f1 have been observed. The relative amounts of the two pre-F1 zones and F1 are higher in the red cells of adults with 97--100% Hb F (homozygous hereditary persistence of fetal hemoglobin, homozygous deltabeta-thalassemia and homozygous beta0-thalassemia) than in the red cells of an adult with homozygous beta+-thalassemia with 66% Hb F, a child with a trisomy-D-13 having 38% Hb F, and in two newborn. Hb F was glycosylated in vitro with [14C]glucose or [14C] glucose 6-phosphate, and was acetylated using chicken reticulocyte lysate or a crude acetyltransferase preparation isolated from the same lysate with [14C]acetyl-CoA as substrate. Chromatographic analyses indicated that the Hb F1 zone can be formed both by glycosylation and acetylation of Hb F, and that pre-F1 zones can be products of the reaction of Hb F with phosphorylated glycolytic intermediates. Biosynthesis of minor hemoglobins in reticulocytes was studied with [14C]leucine in the presence and absence of cycloheximide and by pulse-chase. The resulting data indicate that Hb F1 synthesis is dependent upon Hb F synthesis and that the posttranslational modification may take place at an early stage in Hb F synthesis.
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PMID:On the chromatographic heterogeneity of human fetal hemoglobin. 42 12

Red-cell conversion of pyridoxine to pyridoxal phosphate was studied in control subjects, and patients with heterozygous and homozygous beta-thalassaemia. In 7% of control subjects the rate of pyridoxine conversion was well below the range found in the other control subjects (5.0-8.6%, mean 6.5%/g Hb x 10(-2)) but in heterozygous beta-thalassaemia was below that range in 63% of the patients. The conversion rate was also slow or borderline in the majority of patients with severe transfusion-dependent homozygous beta-thalassaemia, in spite of the presence of some donor cells; but was normal, or fast as in other anaemias, in all but one patient with mild homozygous thalassaemia. There was a much higher incidence of a slow conversion rate in the parents of the severe homozygotes than in parents of the mild homozygotes, illustrating the familial pattern. This supports our view that the red-cell conversion rate of pyridoxine is an inherited characteristic, independent of thalassaemia. The cause of a reduced rate of pyridoxine conversion was investigated. The increase to a normal rate following riboflavin ingestion suggests a defect in the activity of the flavin mononucleotide (FMN)-dependent pyridoxine phosphate oxidase.
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PMID:Abnormal red-cell metabolism of pyridoxine associated with beta-thalassaemia. 43 99

Hematological studies were performed systematically in 101 refugees from South-Eastern Asia living in the Grenoble area at the present time. We found: --4 haemoglobin E homozygosity, --29 haemoglobin E heterozygosity, --2 beta-thalassemia heterozygosity, --4 alpha-thalassemia heterozygosity, --14 glucose 6 phosphate dehydrogenase deficiencies.
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PMID:[Hemoglobin abnormalities and glucose 6 phosphate dehydrogenase deficiency (G6PD) in 101 refugees from southeast Asia]. 75 89

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

Renal function studies were performed in 41 patients with sickle cell-beta thalassaemia (S/b thal) and compared to 14 normal controls and 8 sickle cell (SS) patients. Polyuria, hyposthenuria and mild proteinuria were common in both S/b thal and SS patients. A renal concentrating defect was manifest in all patients studied, and in 4 of the 7 S/b that patients tested, an abnormal acidification test was found. A statistically significant negative correlation (n = 19, r = -0.48, p less than 0.05) was noted between creatinine clearance (CCr) and age for the patients over 30 years. There was no correlation between hemoglobin and CCr; on the contrary, a statistically significant negative correlation was found between CCr and hemoglobin F (n = 29, r = -0.428, p less than 0.05) Our S/b thal and SS patients showed a decreased daily excretion of sodium, calcium, phosphate and magnesium and lower serum magnesium levels than the controls. One third of the S/b thal patients showed hyperuricosuria, and a statistically significant negative correlation was noted between serum uric acid and its fractional excretion in all S/b thal patients (n = 41, r = -0.450, p less than 0.01). Serum phosphate levels were independent of age. A statistically significant positive correlation was found between the tubular reabsorptive capacity for phosphate and the number of painful crises per year (n = 33, r = 0.836, p less than 0.001). We conclude that renal involvement in the double heterozygous state is as severe as in homozygous sickle cell disease.
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PMID:Renal involvement in sickle cell-beta thalassemia. 138 36

This paper describes the use of high-performance capillary electrophoresis for the separation of globin chains. Adult and newborn haemolysates from normal individuals and children suspected of having thalassaemia were analysed using free zone electrophoresis. Separation of globins was accomplished using a 25 mM phosphate buffer at pH 11.8. Distinct peaks of alpha-, beta- and gamma-chains were resolved within 8 min. The coefficient of variation for within-day and between-day runs was 4.1% and 5.7%, respectively. This method is simple and rapid, and it can be used to screen for thalassaemia and for the clinical study of various haemoglobinopathies.
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PMID:Separation of globins using free zone capillary electrophoresis. 140 Jul 24

The mass concentrations of whole blood reduced glutathione and catalytic activity concentrations of the enzymes, glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glutathione reductase (EC 1.6.4.2) and glutathione peroxidase (EC 1.11.9) were analysed in 25 cases of homozygous beta-thalassaemia, 20 cases of heterozygous beta-thalassaemia and 10 controls. The results showed a significant elevation of reduced glutathione and enzymes of the pentose phosphate pathway in homozygous beta-thalassaemia, indicating the existence of an enzyme-regulated glutathione turnover system in the overt state to combat the augmented red cell membrane damage due to auto-oxidant threat. However, in heterozygous beta-thalassaemia, reduced glutathione was increased, but there was no similar elevation of enzymes except for glutathione peroxidase.
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PMID:Enzymes of the pentose phosphate pathway in glutathione-regulated membrane protection in beta-thalassaemia. 144 62

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Limb deformity and metaphyseal abnormalities in thalassaemia major. 774 45

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.
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PMID:Bone disease in children with homozygous beta-thalassemia. 230 56

In 18 beta-thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)-dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red-cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subjects without family history of thalassaemia. This suggests slower red-cell riboflavin metabolism in thalassaemia families, which may have resulted from selection in combination with thalassaemia by malaria. However, there was a markedly higher incidence of red-cell flavin adenine dinucleotide (FAD) deficiency in thalassaemia heterozygotes than in their normal relatives. This was indicated by higher stimulation of FAD-dependent glutathione reductase (GR) activity by FAD and lower GR activity per red cell, and suggests a marked additive effect by thalassaemia on the red cell FAD deficiency that results from the inherited slow riboflavin metabolism. There is evidence that diversion of FAD to other FAD-dependent enzymes might be an important factor.
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PMID:Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia. 272 60


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