Properties of hemoglobin A and hemoglobin Zurich (beta63 histidine replaced by arginine): quantitative evaluation of functional abnormalities in hemoglobins.
Explore the source record for details and available documents.
Arginine↗
SEARCH · PubMed Health
Results for “HEMOGLOBINS, ABNORMAL”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Hemoglobin Nagasaki (alpha 2-A beta 2-17Glu). A new abnormal human hemoglobin found in one family in Nagasaki. Biochemical studies on hemoglobins and myoglobins. V.
Explore the source record for details and available documents.
Amino Acid Sequence↗
A new abnormal human hemoglobin: Hb Prato (alpha 2 31 (B12) Arg leads to Ser beta 2).
An abnormal human hemoglobin was found in a hemolysate from a 5-year-old healthy child living in Prato (Tuscany, Italy). Strutctural studies demonstrated a previously unreported amino acid substitution, alpha 31 (B12) Arg leads to Ser (this is an alpha 1 beta 1 contact). The new variant has been named Hb Prato. It was unstable in isopropanol and heat-denaturation tests, but has normal functional properties, with respect to whole blood studies. Family studies indicated that the variant had been inherited from the mother, a 39-year-old woman of Sicilian extraction. Hb Prato occurs at 20 and 28% in hemolysates from the boy and woman, respectively.
Adolescent↗
Application of reversed phase high performance liquid chromatography and plasma desorption mass spectrometry for the characterization of a hemoglobin variant.
An abnormal hemoglobin was structurally characterized by use of reversed phase high performance liquid chromatography in combination with plasma desorption mass spectrometry for peptide identification. The study was accomplished using approximately 150 micrograms of hemoglobin and unambiguously demonstrated the variant to be beta 104(G6)Arg----Ser, known as Hb Camperdown.
Amino Acid Sequence↗
Hemoglobin variants with altered oxygen affinity.
To date 88 abnormal hemoglobins have been described with altered oxygen affinities. Of these, 60 variants have high affinity and 28 have low affinity. Twenty-six of these abnormal hemoglobins are chemically unstable. Twenty-seven of the high affinity hemoglobins are associated with erythrocytosis. An equal number are not associated with increased red cell mass. Anemia has been reported with 13 of the low affinity variants; however, the primary cause of the anemia of many may be the concurrent chemical instability. A strong correlaton can be shown for stable variants with altered oxygen affinity between the P50 value of the red cell and the hemoglobin concentration of the affected individual's blood. Hemoglobin variants with altered oxygen affinity can be classified into groups depending upon the amino acid change in specific structural sites. The sites include subunit interfaces, heme contacts, central cavity, DPG binding site, C-terminus, and other external and internal residues. Functional studies of six abnormal hemoglobins, four at the beta 101 residue in the central cavity near the alpha 1 beta 2 interfce, one near the DPG binding site and one at the C-terminus of the beta chain, indicate that the exact explanation of the structure-function relationship in hemoglobin depends upon the specific residue that is altered and the chemical properties of the substituted group. Comparative studies of multiple variants of the same position should provide insight into the role of critical residues in the binding of oxygen by hemoglobin.
Binding Sites↗
Hb Himeji or beta 140 (H18) Ala----Asp. A slightly unstable hemoglobin with increased beta N-terminal glycation.
A fast-moving abnormal hemoglobin found in a diabetic patient was identified as beta 140 (H18) Ala----Asp. It comprised about 40% of the total hemoglobin. The beta N-terminal glycation in the abnormal hemoglobin was estimated to be 3 times as much as that in Hb A in the same blood sample. The abnormal hemoglobin was slightly unstable. Oxygen affinity of the stripped hemoglobin was decreased, but that of red cells from the carrier was slightly higher than normal because of the reduced effect of 2,3-diphosphoglycerate.
Blood Protein Electrophoresis↗
Hemoglobinopathies in the Hamilton region. I. A 4-year survey.
A regional laboratory for the diagnosis and investigation of hemoglobinopathies was established by the Hamilton District Program in Laboratory Medicine in October 1970. Specimens from patients suspected of having a hemoglobinopathy were referred to the regional laboratory from all the hospitals participating in the program. Between October 1970 and October 1974, 3547 specimens were screened for an abnormal hemoglobin and thalassemia; 758 cases of thalassemia, 165 cases of abnormal hemoglobin and 14 mixed cases were diagnosed. Before 1970, 110 cases of thalassemia and 12 cases of abnormal hemoglobin were on record in the Hamilton region. Regionalization of laboratory services provides a more effective means of screening for abnormalities in hemoglobin structure and synthesis and facilitates the opportunity for improving diagnostic procedures.
Asia, Southeastern↗
Reverse phase high-performance liquid chromatography and secondary ion mass spectrometry. A strategy for identification of ten human hemoglobin variants.
Ten abnormal hemoglobins were detected and characterized in individual cases referred to our laboratory for evaluation of hematological problems. Six of these variants were electrophoretically silent and could be detected by reverse phase high-performance liquid chromatography (HPLC) analysis. HPLC was also used to analyze the tryptic peptides of each individual variant. In most of these variants, secondary ion mass spectra of the mixture of the tryptic peptides could reveal the aberrant peptide and predict possible substitution through the mass difference between the normal and abnormal peptide. The mass spectra of the isolated abnormal peptide generally contained sufficient fragment ions to define the position of the amino acid substitution, obviating the need for lengthy sequencing procedures. Combination of the two techniques.
Amino Acid Sequence↗
Blood transfusions leading to apparent hemoglobin C, S, and O-Arab hemoglobinopathies.
CONTEXT: Apparent hemoglobinopathies caused by blood transfusions rarely have been reported in the scientific literature. OBJECTIVE: To interpret the abnormal hemoglobins appearing as small peaks on hemoglobin chromatograms or electrophoresis membranes. DESIGN: In the clinical laboratories of a university hospital and a metropolitan hospital affiliated with a medical school, we interpreted hemoglobin chromatograms and electrophoresis membranes; correlated them with patients' medical, laboratory, and transfusion records; and when possible, identified the abnormal hemoglobin in the donors' transfusion segments. RESULTS: We detected 52 incidences of apparent hemoglobinopathies in 32 recipients caused by blood transfusion, of which 46 were hemoglobin C, 4 were hemoglobin S, and 2 were hemoglobin O-Arab. When first detected, the abnormal hemoglobins in recipients ranged from 0.8% to 14% (median, 5.6%). Multiple transfusions with abnormal hemoglobins occurred in 11 patients with 2 patients receiving hemoglobin C blood 5 separate times. One patient received hemoglobin C and later S, and another patient received C and later O-Arab. CONCLUSIONS: Apparent hemoglobinopathies caused by blood transfusions are far more common than previously reported and represent diagnostic challenges. Misdiagnosis could lead to unnecessary testing, treatment, and counseling. If a hemoglobinopathy from a unit of transfused blood is identified in a recipient, we recommend notifying the donor of that abnormality.
Anemia, Sickle Cell↗
Imbalance in alpha and beta globin synthesis associated with a hemoglobinopathy.
In contrast to findings in the thalasemia syndromes, studies of globin synthesis in subjects with structurally abnormal hemoglobins have generally revealed equal production of alpha and beta polypeptide chains. However, in the present investigation of globin biosynthesis in vitro in blood and marrow from two subjects heterozygous for unstable hemoglobin Leiden, beta6 or 7 Glu --> O, a significant excess of alpha-chain production was revealed. A mother and daughter of northern European ancestry with mild compensated hemolytic anemia were found to have 25% hemoglobin Leiden. Increased hemolysis occurred after the ingestion of a sulfonamide and during infections. Normal levels of hemoglobin A2, 3.0 and 2.7%, and hemoglobin F, 0.8 and 0.6%, were found in the two subjects. Similar percentages of the minor hemoglobins were demonstrated in other family members without hemoglobin Leiden. After incubation of peripheral blood with [(3)H]-leucine, the beta(A)/beta(Leiden) synthesis ratio was 1.3, and the specific activity of beta(Leiden) was 1.3-2 times beta(A). These results indicate preferential destruction of the unstable hemoglobin Leiden. However, in contrast to previous studies of other unstable hemoglobins, there was excess synthesis of alpha-chains. The total beta/alpha synthesis ratio was 0.47-0.63 in peripheral blood and 0.82 in marrow. A pool of free alpha-chains was demonstrated by starch gel electrophoresis and DEAE column chromatography. The synthesis of globin chains was balanced in family members without hemoglobin Leiden. This degree of predominance of alpha-chain synthesis in subjects with hemoglobin Leiden resembles the findings in heterozygous beta-thalassemia. However, the relatively normal hemoglobin content of the cells with this abnormal hemoglobin suggests the possibility of an absolute excess alpha-chain production in the hemoglobin Leiden syndrome.
Adult↗
Hb Oita [alpha45(CE3)His-->Pro]: a new silent hemoglobin variant.
We describe a new alpha chain variant accidentally found in a 49-year-old female living in Usa City, Oita Prefecture, Japan. An abnormally low Hb A1c value of 2.5% (normal range: 4.8-6.3%) was found while she was treated with glucocorticoid for Fisher syndrome. The patient was also diagnosed as having an iron deficiency anemia, but otherwise showed a normal hemogram. An abnormal hemoglobin was not detectable by isoelectrofocusing and high performance liquid chromatographic methods, but appeared as a fast-moving alpha chain abnormality by urea-carboxymethyl cellulose column chromatography of the globin, from which the content of the abnormal hemoglobin was estimated at approximately 20%. The instability test of the hemolysate was normal. Structural studies demonstrated that the abnormal hemoglobin had an amino acid substitution of His-->Pro at alpha45. It is a new variant and was named Hb Oita or alpha45(CE3) His-->Pro. Additionally, sequence analysis showed a nucleotide change from A-->C at the second base in the 45th codon of the alpha2 gene, CAC(His)-->CCC (Pro). The beta/alpha ratio was 0.51 (normal range: 0.9-1.2). Her mother and a son did not have the abnormal hemoglobin variant; her father was deceased and no sample was available to verify the inheritance of the variant in this kindred.
Female↗
Hemoglobin Andrew-Minneapolis (beta 144 (HCl) lysine----asparagine) in a Japanese family.
Hemoglobin Andrew-Minneapolis, an abnormal hemoglobin with an asparagine residue substituted for a lysine at position 144 of the beta-globulin chains, was identified in three members of two generations in a Japanese family. The carriers of hemoglobin Andrew-Minneapolis showed false high levels of hemoglobin A1c, as measured by the standard cation exchange high performance liquid chromatography, and a moderate tendency for erythrocytosis. This family is the first report of this abnormal hemoglobin in Japan.
Adult↗
Heterozygous beta-thalassemia: not infrequent in Mexico.
BACKGROUND: The prevalence of beta-thalassemia in Mexico is not known in detail. METHODS: Data of studies investigating abnormal hemoglobins between September 1987 and November 2000 were analyzed; in addition, data of red-blood-cell indices and clinical features were analyzed in patients identified as carriers of beta-thalassemia. RESULTS: In 1,639 prospective studies looking for abnormal hemoglobins, 429 disclosed some abnormality; of these, 319 cases displayed abnormally high levels of hemoglobin A2, thus consistent with the diagnosis of beta-thalassemia. This hemoglobin abnormality represented 74.2% of all abnormalities, both quantitative and qualitative, of the molecule of hemoglobin. There were 317 heterozygotes and only two homozygotes. We have previously shown that the most frequent cause of anemia as the iatrotropic condition in Mexican mestizos is iron deficiency. We found that iron deficiency is 11.5 times more frequent than beta-thalassemia and that the latter is 1.3 times more frequent than macrocytic/megaloblastic anemia. CONCLUSIONS: beta-thalassemia should not be considered as infrequent in Mexico, and individuals with red blood cell microcytosis and/or hypochromia with or without anemia should be screened for thalassemia.
Anemia, Hypochromic↗
Familial association of primary pulmonary hypertension and a new low-oxygen affinity beta-chain hemoglobinopathy, Hb Washtenaw.
A Hungarian-American kindred with familial primary pulmonary hypertension (PPH) and a new, low-oxygen affinity beta-chain variant hemoglobin, Hb Washtenaw, is described. The index case presented with severe PPH and was found to have the abnormal hemoglobin. Two siblings with the abnormal hemoglobin also demonstrated increased pulmonary artery pressures on exercise echocardiography suggestive of early PPH. The occurrence of PPH and the abnormal hemoglobin could be due to genetic or biochemical factors or simply coincidental. A previous study had described a possible association of an abnormal beta-chain variant hemoglobin, Hb Warsaw, and PPH. It was suggested that the putative gene for familial PPH may be located near the beta-globin gene on chromosome 11. The association of PPH and the beta-chain variant hemoglobin in this kindred adds further support to this hypothesis.
Base Sequence↗
Two different mutations in codon 97 of the beta-globin gene cause Hb Malmö in Sweden.
An abnormal hemoglobin with increased oxygen affinity, Hb Malmö [alpha 2 beta 297(FG4)His-->Gln], was found to cause erythrocytosis in two apparently unrelated Swedish families. Direct nucleotide sequencing of amplified DNA demonstrated a CAC-->CAA substitution in one family and a CAC-->CAG substitution in the other. Both mutations resulted in a His-->Gln substitution in codon 97. This finding prompted us to examine the possible point mutations underlying the different hemoglobin variants reported in the literature.
Adult↗
Hb Leiden-beta (0) thalassemia in a Chinese with severe hemolytic anemia.
The first case of Hb Leiden (alpha2beta2 6 or 7 Glu---O)-beta (0) thalassemia in a young patient with chronic severe hemolytic anemia, which improved after splenectomy, is described. His parents were Chinese. The patient's blood showed no Hb A or normal beta chains when no blood transfusion was given. His mother was heterozygous for beta(0) thalassemia, and his father and brother had a trait for the unstable Hb Leiden. The Hb Leiden level of the father was 22.6% and that of the brother was 19.3%. It is probable that the abnormal hemoglobin in this Chinese family resulted from an independent gene mutation, unrelated to the one found in 2 Caucasian families reported earlier.
Adolescent↗
-G gamma A gamma-Thalassemia and gamma-chain variants in Chinese newborn babies.
The occurrence of gamma-chain abnormal hemoglobins and of gamma-thalassemia in Chinese newborns was evaluated through analyses of the Hb F of over 1,100 babies and of the DNA from one baby and his parents. Gene mapping data identified this baby as a homozygote for -G gamma A gamma-thalassemia, which is caused by a deletion of about 5 kb due to an unequal crossing-over between the -G gamma- and -A gamma- genes. This condition is the same as that observed in Indian and Japanese babies [2,3]. Its gene frequency among babies from the Shanghai area was 0.012. A previously unrecognized G gamma chain variant, Hb F-Shanghai or alpha 2 G gamma 266(E10)Lys----Arg, was observed in one newborn. This variant was not detected by conventional techniques but only by high performance liquid chromatography, as the G gamma 66 Lys and G gamma 66 Arg chains had slightly different chromatographic mobilities. Lys at position gamma 66 participates in contacts with the heme group, and its substitution by another amino acid residue might interfere with physiochemical and/or functional properties. No other gamma-chain variants have been detected except the well-known A gamma T or F-Sardinia chain (f.A gamma T = 0.076).
Chromatography, High Pressure Liquid↗
Distinct phenotypic expression associated with a new hyperunstable alpha globin variant (Hb heraklion, alpha1cd37(C2)Pro>0): comparison to other alpha-thalassemic hemoglobinopathies.
Clinical phenotypes associated with abnormal globin chain biosynthesis may result in thalassemia (deficient quantity) or hemolytic anemia (abnormal hemoglobins). However, the phenotypic expression of hyperunstable hemoglobin variants often includes features of thalassemia, along with variable peripheral hemolysis. Hemoglobinopathies caused by highly unstable beta-chain variants have a dominant thalassemia-like phenotype, in which carriers have a clinical expression of thalassemia intermedia, but highly unstable alpha-globin variants are usually only phenotypically apparent when they interact with other alpha-thalassemia mutations. In a child with clinical and hematological features consistent with beta-thalassemia intermedia, DNA analysis excluded any beta-globin gene mutations but characterized a novel deletion cd37(C2)Pro>0 (Hb Heraklion) in the alpha1 globin gene, in trans to a common Mediterranean nondeletion alpha-thalassemia mutation (alpha(Hph)alpha). The deletion of proline at alpha37(C2) is predicted to result in severe instability of the variant hemoglobin, which on interaction with a synthesis-deficient alpha-thalassemia mutation causes a relatively severe dyserythropoietic anemia, representing an alternative phenotype associated with highly unstable alpha-chain variants. Hb Heraklion is the fourth highly unstable alpha-globin variant that we have observed in patients from Greece and Albania. Two variants involve the alpha2-globin gene: Hb Agrinio (alpha29(B10)Leu>Pro) and Hb Adana (alpha59(E8)Gly>Asp), and two the alpha1-gene: Hb Aghia Sophia (alpha62(E11)Val>0) and (Hb Heraklion a37(C2)Pro>0). Each has been observed on interaction with a different alpha-thalassemia mutation and the phenotypes associated with these highly unstable alpha-variants are presented.
Adolescent↗