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

We describe a new type of gamma delta beta-thalassemia in four generations of a family of Scotch-Irish descent. The proposita presented with hemolytic disease of the newborn, which was characterized by a microcytic anemia. Initial restriction endonuclease analysis of the DNA showed no grossly abnormal patterns, but studies of polymorphic restriction sites and gene dosage revealed an extensive deletion that removed all the beta- and beta-like globin genes from the affected chromosome. In situ hybridization of chromosome preparations with radioactive beta-globin gene probes showed that only one 11p homolog contained the beta-globin gene cluster in the affected family members.
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PMID:Hemolytic disease of the newborn caused by a new deletion of the entire beta-globin cluster. 630 57

A mutation that produces an absolute deficiency of normal beta-major globin polypeptides has been recovered from a DBA/2J male mouse. Most mice homozygous for the deficiency survived to adulthood and reproduced but were smaller at birth than their littermates and demonstrated a hypochromic, microcytic anemia with severe anisocytosis, poikilocytosis, and reticulocytosis and the presence of inclusion bodies in a high proportion of circulating erythrocytes. Mice heterozygous for the deficiency demonstrated a mild reticulocytosis but were not clinically anemic. Analysis of globin chain synthesis in vitro by 3H-leucine incorporation revealed that beta-globin synthesis was nearly normal (95%) in heterozygotes and about 75% of normal in deficiency homozygotes. Molecular characterization of the mutation by restriction analysis revealed a deletion of about 3.3 kb of DNA, including regulatory sequences and all coding blocks for beta-major globin. Based on genetic and hematological criteria, mice homozygous for the mutant allele, designated Hbbth-1, represent the first animal model of beta-thalassemia (Cooley's anemia), a severe genetic disease of humans.
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PMID:A mouse model for beta-thalassemia. 631 5

Heterozygous beta thalassaemia with microcytic anaemia (hemoglobin concentration 77 g/l) has been recognized in a 49 year-old woman of Alsatian extraction. A long history of microcytic anaemia had led to inadequate oral iron treatment before the patient was referred to us because of the persisting microcytic anaemia and iron loading. Indeed the patient also had haemosiderosis with a high transferrin saturation (73%) and markedly elevated ferritinaemia (1,114 micrograms/ml). Ferrokinetic data showed increased plasma iron turnover, early transfer of iron to the liver and evidence of ineffective erythropoiesis. She was treated with desferrioxamine (3 g every three days subcutaneously) and serum ferritin levels gradually decreased together with transferrin saturation. After 15 months serum ferritin and transferrin saturation were within the normal range. Several hypotheses are discussed to explain why this patient had haemosiderosis associated with heterozygous beta thalassaemia. The propositus was found to be HLA-A3, which is strongly associated with idiopathic haemochromatosis. Her sister also carries HLA-A3 with heterozygous beta thalassaemia but she has neither anaemia nor iron overload. Thus double heterozygotism is unlikely in our patient.
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PMID:[Iron overload in a beta thalassemia heterozygote of the intermediate type in a subject of Alsation origin. Results of iron chelation treatment]. 633 73

Alpha thalassaemia as a cause of hypochromic, microcytic anaemia in pregnancy is described. The problems associated with accurate diagnosis of this condition and prediction of fetal outcome is now made much easier by use of recombinant DNA techniques such as gene mapping. Two Greek Cypriot families with alpha thalassaemia have been studied by DNA mapping. Definitive assessment of alpha thalassaemia genotype in these cases enabled confident genetic counselling.
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PMID:Alpha thalassaemia in pregnancy. 658 60

The number concentration of erythrocytes in blood (RBC) and the discrimination functions MCV/RBC, (MCV)2 X MCH, DF = (MCV/fl) - (RBC/10(12).1(-1] - (8.1 X Hb mmol.1(-1] - 3.4 have been advocated as useful methods in screening programmes for thalassaemia. In the present work we attempted to estimate the value of each of these methods in screening programmes for thalassaemia and/or iron deficiency and in differentiating between these two conditions. One hundred and twenty-six subjects suffering either from iron deficiency anaemia or heterozygous beta, delta beta, 'silent' beta and alpha 1 thalassaemia were classified by using these methods. Forty healthy subjects served as controls. The RBC was greater than 5.5 X 10(12)1(-1) in 80% of the cases, the three discrimination functions were 'positive' in 91%, 94% and 92% respectively. MCV/RBC and (MCV)2 X MCH separated successfully the subjects with microcytic anaemia (heterozygous thalassaemia and iron deficiency) from normal controls. On the other hand the DF turned out to be more satisfactory than RBC in discriminating heterozygous thalassaemia from iron deficiency anaemia. Thus in population screening for thalassaemia either MCV/RBC or (MCV)2 X MCH ought to be used first and then the DF.
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PMID:Screening for thalassaemia and/or iron deficiency: evaluation of some discrimination functions. 670 45

Patients with thalassemia as well as those with iron deficiency typically have red cell microcytosis and hypochromia. In view of the large number of children with microcytic anaemia or an isolated microcytosis seen at the Red Cross War Memorial Children's Hospital, the frequency with which a low red cell mean corpuscular volume (MCV) was associated with the presence of thalassaemia or with an abnormal haemoglobin was investigated. Of 730 patients with an MCV of 60 fl or less, 46 (6.4%) were found to carry the beta-thalassaemia gene and 20 children (2.7 %) had an abnormal haemoglobin, most commonly haemoglobin E. The prevalence of thalassaemia was greatest among Coloured patients and abnormal haemoglobins were found exclusively in this group of children. The implications of these findings are discussed.
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PMID:Microcytic anaemia and haemoglobinopathy in Cape Town children. 711 19

An 11-year-old boy was noted to have microcytic anemia, growth retardation, polyclonal hypergammaglobulinemia, and abnormal platelet function. An angiomatous lymphoid hamartoma was removed from the retroperitoneal space. Postoperatively the child exhibited a dramatic growth spurt and complete resolution of the abnormal laboratory measurements. Studies were performed before and after tumor removal to investigate the nature of the associated anemia, growth retardation, and altered hemostasis. There was no evidence of iron deficiency, thalassemia, or an antierythropoietin factor. Prolonged bleeding time and impaired ristocetin-induced platelet aggregation normalized following tumor resection. Serum obtained before surgery inhibited lymphocyte proliferation in mixed lymphocyte culture as well as fibroblast growth in vitro. Detailed study of growth regulatory hormones failed to reveal significant alterations except for significantly reduced somatomedin which normalized after surgery. The factor(s) which inhibit in vitro cellular growth and lower in vivo plasma somatomedin concentration remain unknown.
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PMID:Angiomatous lymphoid hamartoma: inhibitory effects on erythropoiesis, growth, and primary hemostasis. 726 91

Ten newborn infants, all belonging to one family, suffered from severe hemolytic anemia. Four babies died shortly before or after birth, six recovered (one spontaneously, 5 after one or more exchange transfusions). In 5 out of 8 patients a mixed hyperbilirubinemia was observed in the immediate postnatal period, with elevated levels of indirect- as well as direct-reacting bilirubin. After the neonatal period, a slight hypochromic, microcytic anemia persisted, without icterus but with decreased osmotic fragility of the erytrocytes and with target cells in the blood smear. The same hematological picture was observed in one of the parents of each affected baby. All anemic adults belong to one large family; therefore, a dominant mode of inheritance is most likely. Although the hematological findings are suggestive for beta-thalassemia normal HbF and HbA2 levels were observed. In vitro incorporation of radioactive leucine into globin chains in reticulocytes demonstrated defective synthesis of beta chains in the affected adults; in two affected infants the same technique showed defective gamma-chain synthesis as well. Analysis of the hemoglobin genes proved that the affected family members are suffering from heterozygous gamma-delta-beta-thalassemia, as originally described by Kan et al. (1972).
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PMID:[Hemolytic disease of the newborn and chronic hypochromic microcytic anemia in one family: gamma-delta-beta thalassemia]. 733 Aug 40

Three mouse strains have been evaluated as suitable models for investigations into the pathogenesis of iron-overload syndromes. Mice with hereditary heterozygous alpha-thalassaemia had moderately raised reticulocyte counts, but were not anaemic and showed little, if any, iron loading. In contrast, mice with homozygous beta-thalassaemia showed microcytic anaemia, reticulocytosis and splenomegaly. Iron-loading was marked, progressive with age and mainly confined to the spleen. Liver iron-loading increased until the age of 7-8 weeks, with no further increase over successive weeks. Although intestinal iron absorption was modestly increased due to enhanced mucosal uptake, the majority of the 'excess' liver and spleen iron could be accounted for by re-distribution of iron from the erythrocytic compartment. Homozygous hypotransferrinaemic mice, with approximately 1-2% of normal plasma transferrin levels, were markedly anaemic with hypochromic microcytic erythrocytes. Intestinal iron absorption increased 3-4-fold (predominantly due to changes in mucosal transfer), as compared to wild-type controls and heterozygotes, and was ascertained to be a major factor causing the marked hepatic iron overload. Heterozygous hypotransferrinamic mice, with over half normal plasma transferrin levels and a mild degree of hepatic iron loading, showed very similar characteristics to wild-type controls. Thus, of the three models, hpx/hpx mice showed the greatest enhancement in intestinal iron absorption and net iron-loading and provides a suitable animal model of spontaneous iron-overload. Comparison of iron absorption values between the models suggests that reticulocytes cannot account for the enhanced absorption seen in the hpx/hpx mice.
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PMID:Intestinal iron absorption studies in mouse models of iron-overload. 801 25

Investigation of microcytic anemia with normal ferrous status in two members (father and daughter) of a Swiss family originating from Bern revealed high levels of HbA2 (4%, 7.3%) and HbF (3.2%, 3.1%). Direct sequence analysis of asymmetrically amplified DNA showed the ATG-->ACG mutation in the intiation codon of the beta-globin gene. Heterozygous beta-thalassemia was not found in either of the propositus's parents or in any of his brothers and sisters. Extended restriction fragment length polymorphism haplotyping of the beta chromosomes led us to the conclusion of a recent spontaneous mutation in the paternal germ cell. The results of routine HLA and blood group testing supported the stated paternity. We also found that the intragenic sequence polymorphisms (frameworks) are not always in linkage disequilibrium with the Bam HI polymorphism downstream from the beta-globin gene as previously observed. This is the second family found to carry this initiation codon mutation in the beta-globin gene. Unlike the first reported family, of Yugoslavian origin, our patients have high HbF levels and this in the absence of a C-->T substitution at -158 site 5' to G gamma.
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PMID:De novo initiation codon mutation (ATG-->ACG) of the beta-globin gene causing beta-thalassemia in a Swiss family. 809 43


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