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)

We have collected steady-state laboratory data for over 2600 patients, age 2 years and over, with sickle cell anemia (HbSS), HbSC disease, and HbS-beta(+)-thalassemia. The packed cell volume (PCV) is lower in males than in females until 17 or 18 years of age in HbSS and ages 13 to 15 in HbSC, but then becomes consistently higher in males. After age 40, the PCV falls in HbSS. The steady-state leukocyte count in HbSS is higher than that in normals, blunting the utility of this measurement in the assessment of infection. In HbSC and HbS-beta(+)-thalassemia, the leukocyte counts are more often within the range of normal. Platelet counts in HbSS are often found to be above normal and show a downward trend with age. There is a progressive rise in creatinine with age. In HbSS, this rise begins at age 14 and may be accounted for by the increased muscle mass that occurs with puberty. The further deterioration of renal function in patients over 20 may be a result of the known adverse effects of sickle cell disease upon the kidney. Our data provide a basis to compare perturbations caused by intercurrent complications and new therapies, as well as to contrast with similar information from other populations of patients with sickle cell disease.
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PMID:Laboratory profile of sickle cell disease: a cross-sectional analysis. The Cooperative Study of Sickle Cell Disease. 162 72

In human red cells, Ca is mainly bound to the inner side of the plasma membrane. A smaller part may be present within intracellular Ca storing vesicles, while only a few percent of total red cell Ca is in ionized form. In some hemolytic anemias (sickle cell anemia, beta-thalassemia), an increased number of endocytotic vesicles storing Ca is probably responsible for the elevation of total red cell Ca content. Red cell Ca inward transport, which is partially susceptible to inhibition by Ca entry blockers, has been reported to be enhanced by physiological shear stress and enrichment in membrane cholesterol, as well as in some hemolytic anemias. Normal intracellular ionized Ca levels have been assessed in several diseases where elevated Ca inward transport rates or decreased Ca efflux through the Ca pump (hemolytic anemias, cystic fibrosis, essential hypertension) had been observed previously. Thus, red cell Ca homeostasis is apparently capable of keeping ionized Ca levels within the physiological range of 20-60 nM under most pathological conditions investigated so far. Conceptually, changes in red cell Ca homeostasis (or also in other red cell membrane parameters) may be of pathophysiological importance in two respects: 1) A disturbance may be directly responsible for some of the symptoms associated with a disease. This is the case in sickle cell anemia, where red cell dehydration is possibly caused by transient elevations of intracellular ionized calcium, which may activate K efflux through the Ca-activated K channel. The presence of dehydrated red cells will, in turn, lead to microvascular occlusion, a pathophysiologically important phenomenon in sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium homeostasis of human erythrocytes and its pathophysiological implications. 164 22

The clinical features of sickle cell disease (SCD) in Saudi Arab children of eastern origin are presented. One hundred and seventy-three children were diagnosed at birth and followed prospectively from 3 months to up to 4 years of age. There were 87 boys and 86 girls. Genotype distribution included 146 sickle cell anemia, 24 sickle beta +-thalassemia, two sickle beta 0-thalassemia, and one sickle hemoglobin C disease. Of our patients, 7% presented in the first 12 months of age and 27% remained asymptomatic at 4 years. Painful crises of bones and joints were the most common initial symptoms, followed by dactylitis, abdominal crises and acute splenic sequestration (ASS), occurring in 60%, 31.6%, 6.7%, and 1.7% of the patients, respectively. None of the patients presented with severe bacterial infections. During this study, 175 sickle cell crises were documented, but only 16 (9.1%) required hospital admissions. There were no deaths in this series. High hemoglobin F levels correlated with delayed clinical presentation and reduced number of crises. We conclude that SCD in children of eastern origin is clinically milder than earlier descriptions from the Eastern Province of Saudi Arabia.
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PMID:Clinical features of sickle cell disease in eastern Saudi Arab children. 168 68

Interferon-gamma (IFN-gamma) has been shown to influence globin gene expression in cord blood and normal adult progenitor-derived erythroblasts. To explore the influence of IFN-gamma on fetal hemoglobin (HbF) synthesis in the hemoglobinopathies, erythroid progenitors (BFU-E, burst forming unit-erythroid) from patients with sickle cell anemia (SCA) and thalassemia were co-cultured with or without IFN-gamma. Hemoglobin content in progenitor-derived erythroblasts was assessed by radioligand assay (RIA). Co-culture of erythroid progenitors from 12 SCA patients with 200-400 U/ml of IFN-gamma resulted in a significant decrease in picograms of HbF and percent HbF per BFU-E-derived erythroblast. The mean decrease (+/- SEM) of picograms of HbF per cell and percent of HbF was by 42 +/- 9% and 35 +/- 8% of control cultures, respectively. Co-culture of erythroid progenitors from 10 patients with thalassemia major or thalassemia variant (HPFH/thalassemia, sickle/beta 0-thalassemia) with 200 U/ml IFN-gamma also resulted in a significant decrease in picograms and percent of HbF per BFU-E-derived erythroblast. IFN-gamma treatment also inhibited the enhancement in gamma-globin synthesis induced in culture by butyric acid. Erythroid progenitors from 2 patients with SCA, 1 patient with sickle/beta 0-thalassemia, and 1 patient with HbE/beta 0-thalassemia were co-cultured with IFN-gamma, L-alpha-amino-n-butyric acid, or both. HbF content (expressed as picograms HbF/cell) was decreased in samples co-cultured with IFN, increased in cultures with L-alpha-amino-n-butyric acid, but remained at control values in cultures treated with IFN plus L-alpha-amino-n-butyric acid. These data demonstrate that IFN-gamma is an environmental factor that influences gamma-globin gene expression in the beta hemoglobinopathies in vitro.
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PMID:Interferon-gamma modulates fetal hemoglobin synthesis in sickle cell anemia and thalassemia. 170 29

Restriction endonuclease analysis was used to detect alpha-gene deletions and to determine the haplotypes in the DNA of the beta S-gene-cluster [Benin, Central African Republic (CAR), and Senegal] in 221 patients with sickle cell anemia (SS). The clinical expression of SS was modified by the beta S-gene-cluster polymorphisms and the alpha-gene status (alpha-thalassemia-2). The overall risk of soft tissue organ failure caused by the obliterative sickle vasculopathy (including stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death) was increased threefold in those with a CAR haplotype and was decreased in those with a Senegalese chromosome (p = 0.003). In the presence of a Senegalese haplotype, the patient's health is better, and with the CAR haplotype it is always worse. With the Benin, it is intermediate. Acute recurrent clinical events including hospitalized sickle cell crisis, bone infarction, and infection are decreased in frequency in those with a Senegalese haplotype. The risk of most acute events including acute chest syndrome is equivalent in those with Benin or CAR haplotypes. In the United States, alpha-thalassemia-2 is co-inherited randomly among the beta S-gene-cluster haplotypes. Acute events occurring during childhood are minimally effected by this co-inheritance. The risk of soft tissue organ failure is decreased. After the age of 20 years, painful episodes of the lumbar dorsal area are increased in patients who had alpha-thalassemia-2 in association with degenerative bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta S-gene-cluster haplotypes in sickle cell anemia: clinical implications. 170 Jun 39

This study was conducted on sickle cell anaemia (SCA) patients from the south-western province (SWP) of Saudi Arabia to determine the effect of thalassaemias, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and Hb F level on the clinical presentation of sickle cell anaemia. The results showed that associated alpha-thalassaemia improved the haematological parameter values while associated G-6-PD deficiency and high Hb F level did not play a significant role in amelioration of the disease in these patients. Hb S/beta(0) -thalassaemia cases showed a severe anaemia similar to the SCA patients without alpha-thalassaemia. However, considerable improvement of the haematological parameters were found in patients with S/beta(0)-thalassaemia and associated alpha-thalassaemia. This paper reveals that alpha-thalassaemia may partially ameliorate the clinical manifestations of SCA in Saudi patients from the SWP, while high Hb F level and G-6-PD deficiency do not modify SCA to any statistically significant extent.
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PMID:Effect of alpha thalassaemia, G-6-PD deficiency and Hb F on the nature of sickle cell anaemia in south-western Saudi Arabia. 170 30

Identification of the beta s-gene-cluster haplotype and alpha-gene status provides a useful tool for the detection of the high-risk SS patient. The DNA polymorphisms of the beta s-gene-cluster modulate the clinical course in sickle cell anemia, especially as it involves the risk of end stage organ failure of the kidney, lung, brain, eyes, bones, and leg ulcers. This is schematically represented in Figure 4. The disease severity is modified according to the beta s-gene-cluster haplotypes and the co-inheritance of alpha-thalassemia-2. In both Africa and America, the CAR beta s haplotype increases the risk of developing an irreversible complication at an early age. The rate of progression of organ damage is regulated by the beta s-cluster haplotype from birth. The preservation of G gamma Hb F is haplotype dependent and correlates with the overall clinical course of the patient. Further modulation of the clinical course with the co-inheritance of alpha-thalassemia-2 tends to decrease the risk of soft-tissue organ failure and increase the risk of osteonecrosis. Epidemiologic studies in Africa together with clinical correlative analysis in Southern California show that SS patients with a Ben haplotype have a less severe illness than those with a CAR and a more severe illness than those with a Sen. A single individual can be expected to fit into the overall pattern. Some sickle related illness will eventually occur in all. The variable clinical manifestations in sickle cell anemia are modified according to the interaction of alpha gene deletions and the beta s-gene-cluster haplotype, are distinct for each organ, and markedly influence the age of onset of end stage major organ failure. In the presence of a Senegal haplotype, the patient's health is better; with the CAR haplotype, it is always worse; severity is intermediate in the Benin haplotype.
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PMID:Beta s-gene-cluster haplotypes in sickle cell anemia. Clinical and hematologic features. 171 10

During the past 15 years there have been remarkable advances in our understanding of the molecular biology of hemoglobin synthesis and the abnormalities in hemoglobinopathies and thalassemia. The globin genes were among the first mammalian structural genes that were cloned and the DNA sequence of the human globin gene clusters has since been completely delineated. During the last ten years, we have also learned of the many deletions and point mutations that give rise to hemoglobin-opathies and thalassemia. In addition, the sequences that control erythroid specific expression of the globin gene has also been revealed. These findings have contributed to our understanding of the pathophysiology of the diseases and have allowed the institution of accurate DNA diagnostic methods to be applied to prenatal diagnosis. As increased fetal hemoglobin synthesis is known to ameliorate the severity of the disease in disorders such as sickle cell anemia and thalassemia, agents which increase the level of fetal hemoglobin synthesis are being tested. Also, the discovery of DNA sequences and transacting factors which are responsible for high erythroid globin gene expression [4] may provide more effective means of gene therapy.
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PMID:Molecular biology of hemoglobin: its application to sickle cell anemia and thalassemia. 172 57

A family case report of sickle cell-thalassemia syndrome shows three problems concerning this disease. Firstly, the problem of differentiating sickle cell-thalassemia from the sickle cell disease; secondly, the wide range varieties in clinical picture; thirdly and finally contradiction in the criteria of prognosis. In this report sickle cell-thalassemia case was confirmed by constructing a hemoglobin electrophoresis pedigree for the patient. Clinical varieties and prognosis of sickle cell-thalassemia in this family are discussed.
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PMID:Sickle cell-thalassemia in a Jordanian family. 175 Jan 38

The levels, structure and composition of plasma lipoproteins were determined in 67 patients with homozygous beta-thalassaemia and compared to healthy or heterozygous members of the same families and to patients with either sickle cell or iron deficiency anaemia. Plasma total and LDL and HDL cholesterol levels were low in patients with homozygous beta-thalassaemia and with sickle cell anaemia. Plasma triglycerides did not differ between subjects. The low plasma and lipoprotein cholesterol was independent of age, transfusion requirements and splenectomy. Abnormal structure and composition of lipoproteins was found in homozygous beta-thalassaemia. The LDL was of higher density and was triglyceride-rich and cholesterol ester-poor. HDL separated to three populations. HDL2 was prominent (in spite of low plasma HDL cholesterol). HDL3 was of normal density and an intermediate HDL population, not found in normal subjects, was identified and designated HDL2-3. All three HDL populations were enriched with triglycerides and poor in cholesterol ester content. The modified LDL and HDL particles may then be possibly cleared rapidly from the plasma by activated monocytes and macrophages.
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PMID:Abnormal low and high density lipoproteins in homozygous beta-thalassaemia. 175 76


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