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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2--6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in alpha globin production with an average alpha/beta ratio of 0.31 (range 0.22--0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either alpha-thal-1 (average MCV 65.2 fl; range 59--70) or alpha-thal-2 (average MCV 79.6 fl; range 74--88). A subject with altha-thal-1 trait had an alpha/beta ratio of 0.56; the average for five cases of alpha-thal-2 was 0.73. One other family member was thought to be homozygous for alpha-thal-2 trait and exhibited an MCV of 65 fl with an alpha/beta ratio of 0.5. These data reconfirm that in Blacks with alpha thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in alpha and beta globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater alpha globin production in that population of thalassaemics.
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PMID:Alpha thalassaemia in American blacks: a study of a family with five cases of haemoglobin H disease. 42 29

Globin mRNAs were isolated from circulating reticulocytes both from rats carrying a homozygous, recessive mutation causing a severe thalassemia-like syndrome and from normal rats. After first identifying the rat globin chains as alpha or beta chains, the translational products primed by both polysomal and nonpolysomal mRNAs in wheat germ 30000 x g supernatant were analyzed: the ratio of alpha to beta globin mRNAs found in polysomes isolated from mutant rats is identical to the ratio of their products synthesized in vivo while the ratio of these mRNAs is quite different in the nonpolysomal fraction, the latter being enriched in alpha globin mRNA. No difference is found in the ratio of alpha and beta globin mRNAs in the polysomal and nonpolysomal RNA isolated from normal rats, both being identical to the ratio of their products synthesized in vivo. One third of the total amount of mRNA found in mutant cells is not in polysomes as compared to only 6 percent for the mRNA from normal lysates. These results suggest that a translational control mechanism is involved although the decreased globin synthesis in b/b anemia can not be fully accounted for by its operation.
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PMID:Rat b/b anemia: translation of normal and anemic globin mRNA in wheat-germ cell-free system. 100 56

The hematology and pathophysiology of sickle cell disease during the postnatal development of younger hemoglobin (Hb) S homozygotes (SS) could be considerably affected by a variability of alpha globin gene numbers. We have documented longitudinal developmental changes of hematological values and hemoglobin composition on 147 patients with SS (alpha alpha/alpha alpha), 64 with SS (-alpha/alpha alpha), and 9 with SS (-alpha/-alpha) between the ages of 1 and 15 years. Non-steady-state data were excluded from these analyses. The number and organization of alpha globin genes was established by gene mapping. As anticipated, mean corpuscular volume and erythrocyte counts correlated with alpha globin gene numbers throughout the 15-year age interval. On the other hand, SS children with alpha alpha/alpha alpha, -alpha/alpha alpha, -alpha/-alpha had similar hemoglobin concentrations up to the ages of 5-10 years. Around the age of 7, the SS patients with -alpha/-alpha developed a higher Hb concentration than that of the SS (-alpha/alpha alpha), which in turn was higher than that of the SS (alpha alpha/alpha alpha). The emergence of this difference coincided with a developmental increase of the mean corpuscular hemoglobin concentration (MCHC) in patients with SS (alpha alpha/alpha alpha) and the decline of Hb F % under 15%. This newly observed developmental change of the MCHC could lead to increased hemolysis and anemia after the age of 5-10 years. It occurs to a smaller extent among SS (-alpha/alpha alpha) or not at all among SS (-alpha/-alpha) such that these two categories of patients have less severe hemolysis and higher hemoglobin levels at older ages. Although the proportion of Hb F was independent of alpha globin gene numbers, the absence of Hb Bart's suggested that alpha-thalassemia promotes the intracellular assembly of Hb F over Hb S tetramers. Thus, the interaction of alpha-thalassemia and Hb F in young SS patients may be more complex than revealed by Hb F levels in cell lysates. Among older SS children (greater than 7 years) alpha-thalassemia and Hb F levels exceeding 15% appear to have additive effects in diminishing the rate of hemolysis.
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PMID:Effects of alpha-thalassemia-2 on the developmental changes of hematological values in children with sickle cell disease from Georgia. 244 97

The haemoglobinopathies are a group of autosomal recessively inherited diseases that are common among populations in the Mediterranean, in Africa and large parts of Asia. In Germany, the immigration of people from those parts of the world has resulted in an increased occurrence in particular of beta thalassaemia. Homozygous patients usually become transfusion dependent during the first year of life as the excess of alpha globin chains in the erythroid precursors causes a most severe dyserythropoietic anaemia. Genetic determinants that diminish the alpha globin chain excess are thus clinically significant. Here, we describe the molecular genetic changes that result in an increased gamma globin gene expression and hende in a binding of alpha globin chains as HbF. We discuss the significance of those changes for the clinical course of beta thalassaemia and for the elucidation of the ontogenetic processes of gene regulation during the perinatal haemoglobin switch.
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PMID:[The molecular basis of hereditary persistence of fetal hemoglobin (HPFH). Clinical importance of the hemoglobin switching mechanism with special reference to Corfu delta beta zero thalassemia]. 246 59

Twelve members of a Maori family were investigated for alpha-thalassaemia after a provisional diagnosis of thalassaemia had been made on the basis of chronic hypochromic microcytic red cell indices. Ten family members were shown to have the 3.7 kb deletion form of alpha-thalassaemia; two of these were homozygous for this deletion (-alpha/-alpha); eight had the single deletion (-alpha/alpha alpha). While anaemia was not a significant finding, the degree of hypochromicity and microcytosis correlated well with the alpha globin gene status of individual family members. This and other studies provide evidence that alpha-thalassaemia is a significant contributor to the chronic mild anaemia of the Maori.
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PMID:Alpha thalassaemia in the Maori: a family study. 247 Nov 23

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

Microcytic red cells from a 70 year old Negro man with mild anemia contained only hemoglobin G-Philadelphia. Red cells from all of his children had low-normal MCV's, and contained 32-34 percent of the abnormal hemoglobin. Oxygen affinity of his blood and stability of his hemolysate were normal, suggesting that his mild anemia was not caused by the the abnormal hemoglobin. Restriction endonuclease analyses of DNA from the proband and his offspring showed that the alpha G-Philadelphia globin gene exists in only one copy per chromosome. The new gene was probably created by an unequal cross-over which deleted an alpha globin coding sequence (derived from one or both alpha globin genes), as well as some or all of the DNA sequence between those genes.
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PMID:Homozygous alpha thalassemia/Hb G Philadelphia. 629 2

In this study we used restriction endonuclease mapping to characterise the molecular defect responsible for haemoglobin H disease in 14 Sardinian children. The resulting genotypes were then correlated with the respective clinical and haematological phenotypes. We found that patients with the combination of non-deletion alpha(+)-thalassaemia [(alpha alpha)th] and deletion alpha(0)-thalassaemia (-Med) have a more severe phenotype than that resulting from the interaction of deletion alpha(0)-thalassaemia (-Med) and alpha(+)-thalassaemia (-alpha) determinants. Clinically, presentation was earlier and with moderate anaemia or haemolytic crisis, enlargement of the liver and spleen, and thalassaemic bone changes. Haematologically, the anaemia was more severe and there were higher bilirubin levels, reticulocyte counts, Hb H levels, and percentage of red blood cells with inclusion bodies. These results suggest that in those Hb H disease patients with the non-deletion [(alpha alpha)th] determinant, two alpha globin genes produce fewer alpha globin chains than a single alpha globin locus.
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PMID:Phenotype-genotype correlation in haemoglobin H disease in childhood. 631 63

The frequency of alpha thalassemia in SR Macedonia was determined with studies of Hb Bart's in 1.140 newborn babies. Hb Bart's was found in 83 infants. Distribution of the levels of Hb Bart's in these neonates, as determined by column chromatography on CM Sephadex, was trimodal. The mean values for Hb Bart's in the three groups were 0.5% (SD = 0.22), 1.61% (SD = 0.48), and 4.88% (SD = 0.81). The first group is believed to result from asynchronism of the neonatal "switch off" of gamma chains and activation of beta chain production. The second and the third group represent alpha thal2 and alpha thal1, respectively. Thus, the incidence of beta thal2 in SR Macedonia is 2.4%, and that of alpha thal1 0.8%. Hb H disease was found in three out of 16.000 school children. This form of alpha thalassemia was also found in five out of 2.800 patients examined for the course of anemia. Biosynthetic studies of family members of the eight individuals with Hb H disease showed that one parent is heterozygous alpha thal1 while the other is heterozygous alpha thal2. All individuals with alpha thalassemia had a reduced rate of synthesis of the alpha chains. The mean alpha/beta total activity ratio in individuals with Hb H disease was 0.51 (+/- 0.08), in heterozygous alpha thal1 0.74 (+/- 0.06), and in heterozygous alpha thal2 0.86 (+/- 0.06). Experiments with in vitro translation of globin mRNK isolated from patients with Hb H disease showed lower alpha/beta ratios (0.06) than the intact cell ratios. These results support previously published data that in Hb H disease and alpha thalassemia trait, there is quantitative deficit in alpha globin mRNK, which is a consequence of deleted alpha globin genes.
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PMID:[Alpha thalassemia in Macedonia]. 734 57

Hemoglobin H disease usually occurs as a result of inheritance of the genes for alpha thalassemia; however, occasionally patients acquire hemoglobin H in association with hematologic malignancy. This report concerns a 63-year-old Filipino man with a myeloproliferative syndrome with marked thrombocytosis and apparently acquired hemoglobulin H disease. The patient had hemolytic anemia, dimorphic red blood cells (RBC) and abundant ringed sideroblasts in the marrow. The peripheral blood contained 27% hemoglobin H and about two-thirds of his RBC had hemoglobin H inclusion bodies. There was no previous history of anemia or evidence of thalassemia in two siblings or nine adult children of the patient. In vitro studies of globin chain synthesis documented markedly decreased production of alpha globin with alpha/beta biosynthetic ratios of 0.05 in peripheral blood reticulocytes and 0.10 in bone marrow cells. The relative concentration of mRNA for alpha globin was approximately 20-fold less than that of beta globin, apparently accounting for the deficiency in alpha globin synthesis.
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PMID:Myeloproliferative syndrome with sideroblastic anemia and acquired hemoglobin H disease. 735 Oct 8


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