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)

A further study of the Tgamma-chain in a variety of conditions has revealed its presence in the cord bloods of ethnic groups previously unstudied. Heterozygous newborn average 17-19% Tgamma-chain while the mean value in four presumed homozygotes was 31%. The Tgamma-chain is readily detectable in beta-thalassemia of various ethnic groups (although infrequent in Blacks) as well as in deltabeta-thalassemia. Studies of a few families have provided an opportunity to determine whether or not certain individuals are heterozygous or homozygous for the Tgamma-gene. The Tgamma-chain has not been detected in the human fetal hemoglobin that is synthesized in increased amounts in persons with the hereditary persistence of fetal hemoglobin. Although the Tgamma-chain is detectable in sickle cell anemia, its frequency appears to be lower than in normal individuals. By focusing upon the relationship of the percentage of Tgamma-chain to the sources of human fetal globulin from determinants in cis and in trans, the conclusion has been reached that the Tgamma-chain is the product of a mutant Agamma-locus which should be named the TAgamma-chain.
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PMID:Further studies of the frequency and significance of the Tgamma-chain of human fetal hemoglobin. 42 52

Because their blood may "unload" oxygen more readily than normal, people with hemoglobin of low oxygen affinity might be expected to be anemic. We have studied a woman with hemoglobin Hope/beta+ thalassemia, whose hemoglobin level was 10.4 to 12.3 gm/dl (normal 14 +/- 2) despite a P50 of 41 mm Hg (normal 26). Her cardiac index was normal, yielding a calculated mixed venous PO2 of 51 mm Hg (normal 34 to 49). Oxygen transport in patients with low oxygen affinity can be maintained by a variety of homeostatic responses, only one of which is altered erythropoiesis.
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PMID:Oxygen transport in a woman with hemoglobin Hope/beta+ thalassemia. 42 43

The case of a girl affected by a Colley's disease of moderate severity is reported. A brother and a sister had levels of Hb F respectively of 18% and 45%. The father showed all the hematological signs of heterozygous thalassemia. The mother, however, was normal so far as osmotic fragility, red cell morphology, and Hb A2 level are concerned. In vitro hemoglobin chains biosynthesis was performed in all the subjects. Both the parents showed an alfa/non alfa ratio typical of beta thalassemia. Therefore, the mother has to be considered a "silent" carrier of the trait. The daughters and the son have a less severe Colley disease originating by such a double heterozygosity.
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PMID:The silent carrier of beta thalassemia: interaction with the typical beta thalassemic trait. 44 85

A Southern Italian patient homozygous for hemoglobin Lepore disease synthesizes approximately 3% Lepore delta beta-globin chains (relative to alpha chains) in the reticulocytes. Measurement of beta-like RNA sequences by hybridization to complementary DNA specific for beta-globin demonstrates a low level (1--2% relative to alpha sequences) of these sequences in cytoplasmic RNA from reticulocytes or spleen cells, suggesting that the Lepore gene is expressed into mRNA at a lower extent than normal alpha or beta genes; the comparison with the level of beta-like sequences found in nuclear RNA (6--8%) further supports this conclusion and indicates, in addition, that Lepore RNA might be degraded at a faster rate than normal. 2--3% beta-like sequences are found in nuclear RNA in three cases of homozygous beta0-thalassemia, setting the highest possible estimate for the delta-RNA level; this figure suggests that the 'delta-promoter'-dependent Lepore delta beta gene is somehow more actively expressed than the delta gene.
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PMID:beta-Like globin RNA sequences in hemoglobin Lepore disease. 44 79

Hemoglobin (Hb) Indianapolis is an extremely labile beta-chain variant, present in such small amounts that it was undetectable by usual techniques. Clinically, it produces the phenotype of severe beta-thalassemia. Biosynthetic studies showed a beta:alpha ratio of 0.5 in reticulocytes and about 1.0 in marrow after a 1-h incubation. These results, similar to those seen in typical heterozygous beta-thalassemia, suggested that betaIndianapolis was destroyed so rapidly that its net synthesis was essentially zero. To examine the kinetics of globin synthesis, reticulocyte incubations of 1.25--20 min were performed with [3H]leucine. The betaIndianapolis:beta A ratio at 1.25 min was 0.80 suggesting that beta Indianapolis was synthesized at a near normal rate. At 20 min, this ratio was 0.46 reflecting rapid turnover of beta Indianapolis. The erythrocyte ghosts from these incubations contained only betaIndianapolis and alpha-chains, and the proportion of betaIndianapolis decreased with time, indicating loss of betaIndianapolis. Pulse-chase studies showed little change in beta A:alpha ratio and decreasing betaIndianapolis:alpha and betaIndianapolis:beta A with time. The half-life of betaIndianapolis in the soluble hemoglobin was approximately equal to 7 min. There was also rapid loss of beta Indianapolis from the erythrocyte membrane. From these results, it may be inferred that betaIndianapolis is rapidly precipitated from the soluble cell phase to the membrane, where it is catabolized. Heterozygotes for beta 0-thalassemia usually have minimal hematologic abnormalities, whereas heterozygotes with betaIndianapolis, having a similar net content of beta-chain, have severe disease. The extremely rapid precipitation and catabolism of betaIndianapolis and the resulting excess of alpha-chains, both causing membrane damage, may be responsible for the severe clinical manifestations associated with this variant. It seems likely that other, similar disturbances in the primary sequence of globin polypeptide chains may produce clinical findings similar to those seen with hemoglobin Indianapolis and thus produce the phenotype of severe beta-thalassemia.
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PMID:Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia. 44 35

The alpha-thalassemia syndromes are a group of inherited anemias, the clinical severity of which has been shown to increase with the number of alpha-globin structural genes deleted. Employing restriction endonuclease gene mapping, we defined the organization of the alpha-globin genes in cellular DNA from Chinese subjects with various alpha-thalassemia syndromes. The four alpha-globin genes of normals are at two loci located on a 23.0-kilobase pair (kb) Eco RI fragment. In deletion type hemoglobin-H disease the 5' alpha-globin locus is deleted and the single 3' alpha-globin locus is found on a 19.0-kb Eco RI fragment. In alpha-thalassemia-2 there are two alpha-globin genes on a 23.0-kb Eco RI fragment and one on a 19.0-kb fragment. In alpha-thalassemia-1 and the nondeletion type of hemoglobin-H disease the two alpha-globin genes are at two loci on one chromosome and none reside on the other chromosome.
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PMID:Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes. 44 45

In the 1976 hemoglobinopathy proficiency testing survey of the Center for Disease Control (CDC), whole-blood samples from hematologically normal adults and from individuals heterozygous for beta-thalassemia were shipped to survey participants. The object of this survey was to determine the state of the art for technics used to quantitate hemoglobin A2 (Hb A2) and to test the ability of laboratories to differentiate between blood samples having normal Hb A2 levels and those having elevated levels (i.e., those from individuals with beta-thalassemia trait). The results of Hb A2 quantitation obtained from 183 volunteer participant laboratories were compared with those obtained from 24 reference laboratories. Individual values varied greatly among laboratories and among methods for both normal and elevated Hb A2 samples. The results returned by many laboratories were not within 2 SD of the reference laboratory mean and also were not sufficiently accurate to differentiate between the normal blood samples and those with beta-thalassemia trait. The results suggest that methods for quantitating Hb A2 need to be standardized and a suitable method for determining laboratory performance found.
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PMID:Quantitation of hemoglobin A2. An interlaboratory study. 45 72

A thalassemia screening program was implemented at our institution using the finding of a mean corpuscular volume less than 80 fl as the index of abnormality. Further evaluation using hemoglobin (Hb) electrophoresis and serum iron studies was carried out according to the scheme detailed below. A diagnosis of thalassemia was made in 33 women (42 pregnancies). Eight patients had alpha-thalassemia trait, 23 beta-thalassemia trait, and two Hb H disease. Thalassemia trait did not have any adverse effect on pregnancy outcome. In two couples the fetuses were at risk for homozygous disease and in one couple the fetus was at risk for sickle cell beta-thalassemia. The screening program described is an effective and inexpensive means of detecting thalassemia in an antenatal population and is applicable to most every clinic or office setting.
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PMID:Thalassemia and pregnancy: results of an antenatal screening program. 46 58

The rarity of hemoglobin (Hb) H disease in combination with sickle trait may be due in part to the absence of actual Hb H in individuals who, nonetheless, have inherited the deletion of three alpha-globin genes. We describe here a boy with persistent microcytic, hypochromic anemia despite adequate iron stores, who exhibited splenomegaly with a normal reticulocyte count and only rare inclusions in circulating erythrocytes. Starch gel electrophoresis and isoelectric focusing at age 5 yr showed 21% Hb S, persistent Hb Bart's, but no Hb H. Recticulocyte alpha/non-alpha globin chain synthesis ratio was 0.58 at age 5. The mother (Asian) had laboratory evidence of alpha-thalassemia trait and the father (Black) had sickle trait. The nature of alpha-thalassemia in this patient was investigated both by liquid hybridization and by the Southern method of gene mapping, in which DNA is digested with restriction endonucleases and the DNA fragments that contained the alpha-globin structural gene identified by hybridization with complementary DNA. The patient had only one alpha-globin structural gene, located in a DNA fragment shorter than that found in normal or alpha-thalassemia trait individuals, but similar to that present in other patients with Hb H disease. Morphologic studies of bone marrow by light and electron microscopy revealed erythroid hyperplasia with inclusions in polychromatic and orthochromatic erythroblasts, suggesting early precipitation of an unstable hemoglobin. The lack of demonstrable Hb H may be the result of both diminished amounts of beta(A) available for Hb H formation (since one beta-globin gene is beta(S)) and the greater affinity of alpha-chains for beta(A) than beta(S)-globin chains leading to the formation of relatively more Hb A than Hb S. The presence of a beta(S) gene may thus modify the usual clinical expression of Hb H disease.
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PMID:Modification of hemoglobin H disease by sickle trait. 47 66

The heterogeneity of residue 136 of the gamma-chain of human hemoglobin has been determined for a patient afflicted with severe alpha-thalassemia. Separation of the cord blood sample into the various constituent hemoglobins A, F, FI and Bart's were done on a column packed with DEAE Sephadex. The amount of glycine or alanine at position 136 was determined for hemoglobins F, FI and Bart's. The ratios determined for all three hemoglobins indicated that the G gamma/A gamma ratio is the same for all three fractions and is similar to that observed in normal cord blood samples.
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PMID:Heterogeneity of fetal hemoglobin in severe alpha-thalassemia. 48 8


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