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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied two members of an African American family with erythrocytosis. An abnormal hemoglobin variant with an electrophoretic pattern on cellulose acetate similar to Hb J was identified. The oxygen dissociation curve using whole blood was biphasic, dramatically left-shifted, and hyperbolic. Sequence analysis of DNA from the proband showed heterozygosity for a T-->A change at the first position of codon 145 in the beta-globin gene which results in the substitution of an asparagine residue for normal tyrosine. The second cycle of C-terminal amino acid sequence analysis of a mixture of alpha- and beta-globin chains showed tyrosine, aspartic acid, and small amounts of asparagine. Collectively, these results indicate the existence of a mutation at codon 145 of the beta-globin gene which encodes for asparagine instead of tyrosine, and that asparagine then undergoes a partial posttranslational deamidation to aspartic acid. This amino acid substitution corresponds to Hb Osler, which is a high oxygen affinity hemoglobin variant, initially described to be caused by a substitution of Tyr-->Asp at beta 145. Posttranslational amino acid modification may constitute an important component in the pathophysiology of hemoglobinopathies.
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PMID:Hb Osler [beta 145(HC2)Tyr-->Asp] results from posttranslational modification. 910 Dec 80

In this report we describe the molecular analysis of 795 chromosomes derived from unrelated Turkish beta-thalassemia and sickle cell anemia carriers identified in hematology clinics in Istanbul, Ankara, Izmir, Adana, and Antalya. The determination of the molecular pathology of 754 beta-thalassemia and 42 abnormal hemoglobin genes and analysis of the frequency distribution in six distinct regions of Turkey was accomplished. The experimental strategy, based on PCR amplification of the beta-globin gene, included dot-blot hybridization with 18 probes specific for the Mediterranean populations, denaturing gradient gel electrophoresis, and genomic sequencing. When the regional results are compared with the overall frequency of mutations in the country, it is observed that the frequencies in the western and southern parts of Turkey are in good accordance with the overall distribution, whereas the northern and eastern parts have a more region/population-specific profile with some rare mutations having a significantly high occurrence in these regions. Further evaluation of the data with respect to region- or population-dependent differences will contribute to a better understanding of the mechanisms leading to the marked genetic heterogeneity in Turkey, but could also be extremely valuable in facilitating rapid identification of mutations in families at risk for different hemoglobinopathies.
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PMID:Molecular and population genetic analyses of beta-thalassemia in Turkey. 949 72

Twelve patients with anemias and their close relatives were examined: 8 adults (3 men and 5 women) and 4 children (3 boys and 1 girl). Six of them were Armenians, 1 woman was Russian, and the rest were of mixed origin: 3 Russian-Azerbaijan-Ukrainian, 1 child Russian-Ukrainian-African, and 1 woman Russian-Ukrainian. Hemoglobinopathies were detected in 10 subjects from 4 families (3 families from Donetsk and 1 from Moscow). Homozygotic beta-thalassemia major (Hb F 98.9%) was diagnosed in a 2-year-old Armenian girl from Donetsk. The girl lags behind in development and suffers from anemia with hepatosplenomegaly and jaundice. Heterozygotic beta-thalassemia minor with increased levels of Hb A2 and Hb F was diagnosed in her parents (Armenians from Azerbaijan). A 15-year-old Russian-Azerbaijan-Ukrainian boy from another family in Donetsk had beta-thalassemia with HbD (94%). The boy suffers from anemia with hepatosplenomegaly, jaundice, and chronic hepatitis. Heterozygotic beta-thalassemia with increased levels of Hb A2 and Hb F was revealed in proband's mother and brother; the father was not examined. alpha-Thalassemia is suspected in a 3-year-old boy from a Russian-Ukrainian-African family in Donetsk; he presented with a very small "fast" abnormal hemoglobin fraction. The boy suffers from anemia with splenomegaly and systolic murmur. Blurred form of thalassemia minor is diagnosed in the mother. The father, an African from Zaire, was not examined. Heterozygotic beta-thalassemia with increased Hb A2 level was revealed in a 20-year-old Armenian boy from Moscow. He presented with manifest splenomegaly, chronic gastritis, and mitral valve prolapse. His mother suffers from thalassemia minor, was anemic during pregnancy, and there are cases of anemia in the family. No hematologic disorders were found in the father. No hemoglobinopathies were detected in a 59-year-old Russian women from the town of Tver with very grave anemia; apparently, her condition was acquired, but not hereditary. Data on patients in the city of Donetsk are of special interest, for there are virtually no reports about hemoglobinopathies in the Ukraine.
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PMID:[Beta-thalassemia and Hb D in patients with anemia]. 957 28

HbOThrace is an abnormal hemoglobin which is constructed by defective beta chains (Glu121-->Lys121). It mostly characterises the Muslim minority of the Thrace region. During the last 6 years, our department detected HbOThrace in 118 cases. Four groups were formed, the first consisted of cases of HbOThrace trait with normal iron and ferritin levels, the second of cases of HbOThrace hemoglobinopathy, the third of cases of HbOThrace/Hb beta zero hemoglobinopathy and the fourth of cases of HbOThrace trait with low iron and ferritin levels. The second, third and fourth group were compared with the first one. The conclusion is that the presence of HbOThrace leads to a mild hypochromic anemia, with no clinical findings, but the coexistence of beta zero gene or iron deficiency produces more pronounced laboratory findings and even clinically evident anemia.
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PMID:HbOThrace trait, HbOThrace hemoglobinopathy and HbOThrace/Hb beta zero hemoglobinopathy: a retrospective study of 118 cases. 1020 93

Unstable hemoglobin disorders are due to substitutions or deletions of amino acids which alter the normal tertiary structure of hemoglobin and/or decrease heme-binding to globin. These changes result in enhanced oxidation to methemoglobin, rapid conversion of methemoglobin to hemichrome and sometimes heme loss, which leads to denaturation and precipitation as Heinz bodies. This process is associated with marked oxidative membrane damage, such as crosslinking of membrane proteins, membrane lipid peroxidation, hemin-induced destabilization of cytoskeletal protein interactions, and increased permeability to potassium ions. The damaged erythrocytes are sequestered in the spleen, where Heinz bodies are "pitted" or the entire cell is phagocytized by macrophages. The precise mechanisms leading to hemolysis are not fully understood. However, one hypothesis involves hemichrome binding to the cytoplasmic domain of band 3, leading to clustering of band 3 in the membrane and immunologic recognition of the redistributed band 3 by autologous senescent antibodies. This theory is based on immunologic findings rather than deformability changes, and it is consistent with many features of unstable hemoglobins.
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PMID:[Effects of abnormal Hb on red cell membranes]. 1022 88

Thalassemia is one of the most common single gene disorders. The geographic distribution of thalassemia and abnormal hemoglobin has been known for many years. A worldwide significant spread of these abnormal genes, especially from Southeast Asia, occurred in the last two decades. This has resulted in a dramatic increase of Hb E disorders and various Southeast Asian thalassemia genotypes, which means that requests for hemoglobinopathy investigations are likely to increase in many laboratories worldwide. Hemoglobinopathy screening and diagnosis may need to be undertaken antenatally, neonatally and in certain hematological situations. The introduction of automation for hemoglobinopathy screening, including the automated cell counting and HPLC system, is an important advance in technology for hematology laboratories. The instruments need to be calibrated and standardized to get an accurate data for interpretation. Internal and external control samples are also needed. Combination of test results is usually required to achieve a proper diagnosis, which in turn, provide a self-check for each laboratory test.
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PMID:Standardization on laboratory diagnosis of thalassemia and abnormal hemoglobin. 1092 67

The semiological value of hemoglobin A1c (HbA1c) as a retrospective and cumulative marker of glycemic balance in diabetic patients is greatly weakened in case of hemoglobinopathy. The presence of an abnormal hemoglobin raises methodological problems due to the interferences generated in most assay methods, but also alters the normal process of HbA glycation to HbA1c, and often induces a certain level of hemolysis, very variable and impossible to quantify. This paper reviews methodological and semiological problems related to the presence of abnormal hemoglobin species, and proposes a standardized strategy in case of hemoglobinopathies.
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PMID:[Hemoglobin A1C determination and hemoglobinopathies: problems and strategies]. 1093 42

The rare hemoglobinopathies with abnormal oxygen binding are usually characterized by erythropoietin-mediated erythrocytosis. Bare et al. first described a hemoglobinopathy with mild erythrocytosis in a 22-year-old Caucasian woman in 1976. These authors called the abnormal hemoglobin Hb York. Hb York is characterized by a mutation at the beta146 position that changes histidine into proline. A second case of Hb York was observed by Kosugi et al. in 1983. To the best of our knowledge, no further cases have been reported. We have encountered a new case of Hb York, which was detected by agar gel electrophoresis at pH 6.0. Analysis of DNA sequences revealed a CAC-->CCC mutation in codon 146. The proportion of Hb York was approximately 50%. Analysis of oxygen transport function showed a leftward shift of the sigmoidal O2-dissociation curve. P50 was reduced to 15.5 mmHg. Investigation of family members revealed Hb York in the patient's sister, two daughters and a grandson. In retrospect, the mother of the patient may also have been affected. The mode of inheritance is autosomal dominant.
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PMID:Hemoglobinopathy York [beta146 (HC3) His==>Pro]: first report of a family history. 1147 52

The content of glycated hemoglobin (Hb A1c) evaluated by high pressure chromatography on a VARIANT analyzer using Hb A1c software correlated with the mean daily blood glucose level in the majority of diabetics with types 1 and 2 disease and helped evaluate the compensation of diabetes mellitus during the latest 2-3 months of observation. Low Hb A1c values in combination with an extra hemoglobin fraction, unidentified by the software we used, were detected in 3 Russian women suffering from type 2 diabetes mellitus, with high blood glucose levels. Application of Hemoglobinopathy software showed an abnormal spectrum of hemoglobin fractions in the blood of all 3 patients: appearance of hemoglobin D paralleled by decrease of Hb A0. The presence of abnormal hemoglobin D in these patients was confirmed by the results of electrophoresis on cellulose acetate films and a negative test for sickle erythrocytes. Abnormal hemoglobins are responsible for discoordination between glucose content and Hb A1c in the blood of diabetics. Measurement of serum fructosamine is recommended for evaluation of diabetes compensation in patients with hemoglobinopathies.
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PMID:[Limits of chromatographic determination of glycated hemoglobin (Hb A1c) in diabetes mellitus in presence of abnormal hemoglobins]. 1153 May 31

Hemoglobin E is very common in parts of Southeast Asia. The possible malaria protective effects of this and other inherited hemoglobin abnormalities prevalent in Thailand were assessed in a mixed erythrocyte invasion assay. In vitro, starting at 1% parasitemia, Plasmodium falciparum preferentially invaded normal (HbAA) compared to abnormal hemoglobin (HbH, AE, EE, HCS, beta-thalassemia E) red cells (HRBCs). The median (range) ratio of parasitization of HRBCs (n = 109) compared to the controls of different major blood groups was 0.40 (0.08, 0.98), less than half that of the normal red cells (NRBCs) compared to their controls 0.88 (0.53, 1.4; P =.001). The median (range) parasitemia in the HRBCs was 2% (0.1%-9%) compared to 5.2% (1.2%-16.3%) in the NRBCs (P =.001). The proportion of the RBC population that is susceptible to malaria parasite invasion can be described by a selectivity index (SI; observed number of multiply invaded RBCs/number predicted). The heterozygote AE cells differed markedly from all the other cells tested with invasion restricted to approximately 25% of the RBCs; the median (range) SI was 3.8 (1-15) compared with 0.75 (0.1-0.9) for EE RBCs (P <.01). Despite their microcytosis, AE cells are functionally relatively normal in contrast to the RBCs from the other hemoglobinopathies studied. These findings suggest that HbAE erythrocytes have an unidentified membrane abnormality that renders the majority of the RBC population relatively resistant to invasion by P falciparum. This would not protect from uncomplicated malaria infections but would prevent the development of heavy parasite burdens and is consistent with the "Haldane" hypothesis of heterozygote protection against severe malaria for hemoglobin E.
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PMID:Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. 1214 84


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