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

To date, more than 35 single or oligonucleotide mutations of the alpha genes that cause alpha thalassaemia have been described. Their interactions give rise to widely variable clinical manifestations, from a mild hypochromic, microcytic anaemia to a lethal intrauterine anaemia associated with hydrops fetalis. Understanding the molecular genetics enables accurate genotyping, genetic counselling and prenatal testing for the most severe forms of alpha thalassaemia. Here we show for the first time that the interaction between two relatively common forms of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)) may be associated with a clinically severe form of alpha thalassaemia, Hb H hydrops fetalis.
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PMID:Hb H hydrops fetalis syndrome associated with the interaction of two common determinants of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)). 1202 55

Hb J Sardegna is a well known innocent Hb variant which is widespread in Sardinia. As yet, homozygosity for Hb J Sardegna has not been documented. This report deals with the homozygous state for Hb J which we demonstrate by molecular analysis in two Sardinian siblings in which beta-thalassemia coexists. The Hb J specific mutation was determined both by enzyme digestion and by sequencing specific segments of PCR amplified alpha-globin genes. A pregnant girl showed mild non-sideropenic microcytic anemia, normal Hb A(2) levels (2.4%) on DE-52 microchromatography, 50% of Hb variant on HPLC and 2.1 alpha/beta globin chain biosynthetic ratio. She proved to be a carrier of the beta degrees 6(-A) thalassemia determinant. The alpha-globin gene mapping did not reveal alpha-thalassemia. Btg I restriction analysis of both alpha(2)-globin genes showed a recognition site defect for this enzyme in both chromosomes, which resulted to be the C-->A point mutation in homozygosity at the first nt of alpha(2)-globin gene 50th codon by sequencing. This defect, typical of Hb J Sardegna, was also present in her brother. From a practical point of view, this study demonstrates that the association of beta-thalassemia with Hb J, may show falsely reduced Hb A(2) levels on routine Hb A(2) quantitation techniques, such as DE-52 microchromatography. This possibility implies that identification methods such as simple Hb electrophoresis, which permit visualization of Hb A(J)(2) should be used in thalassemia screening involving populations in which Hb J and beta-thalassemia coexist.
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PMID:The homozygous state of Hb J Sardegna. 1218 62

Hemoglobin A(2) (alpha(2)delta(2)), a minor (2-3%) component of circulating red blood cells, acts as an anti-sickling agent and its elevated concentration in beta-thalassemia is a useful clinical diagnostic. In beta-thalassemia major, where there is a failure of beta-chain production, HbA(2) acts as the predominant oxygen delivery mechanism. Hemoglobin E, is another common abnormal hemoglobin, caused by splice site mutation in exon 1 of beta globin gene, when combines with beta-thalassemia, causes severe microcytic anemia. The purification, crystallization, and preliminary structural studies of HbA(2) and HbE are reported here. HbA(2) and HbE are purified by cation exchange column chromatography in presence of KCN from the blood samples of individuals suffering from beta-thalassemia minor and E beta-thalassemia. X-ray diffraction data of HbA(2) and HbE were collected upto 2.1 and 1.73 A, respectively. HbA(2) crystallized in space group P2(1) with unit cell parameters a=54.33 A, b=83.73 A, c=62.87 A, and beta=99.80 degrees whereas HbE crystallized in space group P2(1)2(1)2(1) with unit cell parameters a=60.89 A, b=95.81 A, and c=99.08 A. Asymmetric unit in each case contains one Hb tetramer in R(2) state.
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PMID:Crystallization and preliminary X-ray structural studies of hemoglobin A2 and hemoglobin E, isolated from the blood samples of beta-thalassemic patients. 1265 64

Hereditary persistence of fetal hemoglobin (HPFH) is the condition whereby a continuously active gamma-globin gene expression leads to elevated fetal hemoglobin (Hb F) levels in adult life [Stamatoyannopoulos G, Grosveld F. Hemoglobin switching. In: Stamatoyannopoulos G, Majerus PW, Perlmutter RM, Varmus H, eds. The Molecular Basis of Blood Diseases. Philadelphia: W.B. Saunders, 2001:135-182; Wood WG. Hereditary persistence of fetal hemoglobin and delta(beta) thalassemia. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge: Cambridge University Press, 2001:356-388; and Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. In: Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. Oxford: Blackwell Scientific Publishers, 1981:450-507]. The condition is caused either by mutation of the beta- and gamma-globin genes, or the gamma-gene controlled region on other chromosomes. Several families with this condition have been reported from Vietnam, Cambodia and China, and the Southeast Asian mutation (or HPFH-6), a 27 kb deletion, was demonstrated. Here we report on a mother and her daughter of the Karen ethnic group with high levels of Hb F, living in the Suan Pueng District on the border of Thailand and Myanmar. Genotyping showed a heterozygosity for the 27 kb deletion of the beta-globin gene. Their conditions have been confirmed by gap polymerase chain reaction (PCR) with three oligonucleotide primers recently developed by Xu et al. [Xu X-M, Li Z-Q, Liu Z-Y, Zhong X-L, Zhao Y-Z, Mo Q-H. Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with beta-thalassemia in a Chinese family. Am J Hematol 2000; 65:183-188.], and a DNA sequencing method. Thus far there has been no official report of the HPFH-6 anomaly from Thailand. The compound heterozygosity of beta-thalassemia (thal) and hereditary persistence of Hb F causes the phenotype of thalassemia intermedia; in contrast, homozygotes for this anomaly show only mild microcytic anemia. Hence, genetic counseling for hereditary persistence of Hb F carriers is needed for family planning.
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PMID:Molecular characterization of hereditary persistence of fetal hemoglobin in the Karen people of Thailand. 1277 71

Iron deficiency and heterozygous beta-thalassemia are important causes of hypochromic-microcytic anemia. Two laboratory parameters are suggested for the differentiation of such anemia. High-fluorescence reticulocyte counts and soluble transferrin receptor levels were determined in iron-deficiency anemia patients (n = 49) and heterozygous beta-thalassemia patients (n = 43). There was no significant difference in high-fluorescence reticulocyte and soluble transferrin receptor values between the two groups, but a correlation was observed between high-fluorescence reticulocytes and soluble transferrin receptors in iron-deficiency anemia, probably due to increased receptor synthesis as a response to decreased iron content in erythrocytes.
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PMID:Soluble transferrin receptor and immature reticulocytes are not useful for distinguishing iron-deficiency anemia from heterozygous beta-thalassemia. 1287 58

We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, GCC [Ala] --> GAC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.
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PMID:Dominant beta-thalassemia with hemoglobin Hradec Kralove: enhanced hemolysis in the spleen. 1468 90

Laboratory investigation plays a crucial role in the workup of hematological disease. The well established method of morphological analysis of blood components has been continuously complemented by other methods. On one hand, these consist of considerable improvements of methods employed for automated cell enumeration allowing for early and accurate detection of cell subpopulations, and quantification of valuable red cell parameters, which are of use in the differential diagnosis of anemia. On the other hand, several parameters for the differentiation of microcytic anemia have become available often allowing for the sometimes difficult diagnosis of anemia of chronic disease, iron deficiency anemia, or thalassemia (ferritin, soluble transferrin receptor, transferrin saturation, RDW, zinc protoporphyrin, as well as reticulocyte indices CHr, Ret-Y Hypo%). In macrocytic anemia, introduction of methods to measure methylmalonic acid (MMA), homocystein, holotranscobalamin (holo-TC), complement the determinations of vitamin concentrations (vitamin B12, folic acid in serum and erythrocytes). Employing these newer parameters in addition to the well established ones allows for detection of early or combined disease. The clinician has to know the diagnostic characteristics not only of the old but also of the newer parameters.
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PMID:[Conventional and new laboratory parameters in the evaluation of hematologic disease]. 1501 92

Hereditary sideroblastic anemia is a very rare disease recessive and X-linked that affect heme biosynthesis by deficit or decreased of delta aminolevulinic acid synthase (ALAS) activity. We report a case of a six-month-old boy, admitted in the hospital for anemic syndrome. The hemogram showed anemia (hemoglobin: 4.5 g/dL), frankly hypochronic microcytic and a regenerated (mean corpuscular hemoglobin concentration: 26 g/dL, mean cell volume: 53 fl, reticulocytes: 10 x 10(9)/L) with red cells morphologic disorders in smears (anisopoikylocytosis) without attack of the other lineages; white blood cells: 11 x 10(9)/L (neutrophils: 64% and lymphocytes: 35%); platelets: 350 x 10(9)/L. Examination of bone marrow showed an important erythroid hyperplasia (about 69%) with dyserythropoiesis. Perls stain revealed intense siderosis with 90% of ringed sideroblasts and a large number of siderocytes. Exploration of ALAS2 and ABC7 genes on the DNA of the infant was not found abnormalities. Treatment with pyridoxine corrects moderately the anemia. By the way, we proposed to remind that iron deficiency, inflammatory syndrome and thalassemia are the common microcytic anemia. However, it's mandatory to explore other causes if diagnosis is not solved.
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PMID:[Hereditary sideroblastic anemia: a rare diagnosis]. 1521 71

Haemoglobin E is a beta chain variant quite common in Southeastern Asia. The case of a gravid Thai woman with a microcytic anaemia is reported. The diagnosis of homozygous haemoglobin E was suspected on the basis of ethnic considerations when analysis of her haemoglobin showed the absence of normal HbA1 and about 100% of a variant Hb with electrophoretic mobility with HbC and HbA2. Identification of the haemoglobin variant was performed by using an association of alkaline electrophoresis on agarose gel, acid electrophoresis on agarose gel, haemoglobin isoelectrofocusing, high performance liquid chromatography. A study of haemoglobin pattern in the partner, parents and siblings was also performed. Pregnancy continued without any problems until the 40th week when a caesarean section was performed due to a difficult labour with foetal distress. The haemoglobin pattern of the new-born was studied at birth and after 1 year; as expected, it was quite normal at birth and a heterozygous condition for HbE was observed after 1 year. HbE, in even heterozygous and homozygous states, gives a mild clinical picture but its association with other haemoglobinopathies, such as a double heterozygous state (i.e. HbE/beta Thalassaemia) gives rise to a severe transfusion dependent thalassaemia syndrome. It is the authors' opinion that only a strict interaction between obstetricians and pathologists is the possible correct answer to the new diagnostic question proposed by a rapidly evolving inter-ethnic society.
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PMID:Haemoglobin E in pregnancy. A case report. Diagnosis, familiar study and counselling, follow up until delivery and new-born observation. 1525 45

We present two Japanese students with thalassemia identified during screening for anemia in their junior high school. Blood test results revealed marked hypochromic and microcytic erythrocytosis in one patient and microcytic anemia in the other. Both cases showed a mean corpuscular volume/red blood cell (MCV/RBC) ratio less than 13. Their beta/alpha synthesis ratio was elevated. Deletion of psialpha2, psialpha1, alpha2, alpha1 and theta1 genes in the alpha-globin gene clusters were noted in the first case. This pattern of gene deletion was consistent with heterozygous alpha-thalassemia 1 of the Southeast Asian type. On the other hand, an increased hemoglobin A2 level and reduced beta/alpha synthesis ratio were found in the second case. Direct cloning and DNA sequencing identified a point mutation (guanine to adenine) at position 1 of intervening sequence II in the beta-globin gene (IVS II-1 G-->A). These results suggest that this patient had heterozygous beta0-thalassemia. Diagnosis of thalassemia should be confirmed by molecular analysis in cases with microcytic anemia or hypochromic microcytosis with a MCV/RBC ratio of 13 or less.
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PMID:Two children with thalassemia identified during screening for anemia in junior high school. 1532 91


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