ABSTRACT
We describe hematologic data from 18 newborn infants including follow-up data. Of these, ten were the offspring of patients with beta-thal/Hb E disease and the remainder were infants who were found to have a decrease in red cell osmotic fragility during a random cord blood examination. The results of the cord blood study showed that two infants having normal red cell osmotic fragility with about 2% Hb E + Hb A + Hb F at birth represented Hb E heterozygosity. Eleven babies had slightly decreased red cell osmotic fragility, a mild degree of microcytosis and poikilocytosis, and hemoglobin types of Hb A + Hb F with no elevation of Hb A2 at birth. They subsequently had hematologic findings consistent with the beta-thal heterozygosity. The means of hematological values of cord blood in the beta-thal trait infants appeared to be statistically different from those in the normal infants only with respect to increased red cell count and reduced MCH. One infant was thought to have the beta-thal trait but had a greater degree of thalassemic changes in red cells; subsequently he turned out to have homozygous beta-thalassemia. Four newborn infants with hypochromia and numerous target cells had 4-7% Hb E + Hb F without Hb A. Follow-up examination showed two cases of Hb E homozygosity; however, the others, who had obvious microcytosis and poikilocytosis in cord blood, finally developed beta-thal/Hb E disease. Thus, a careful study on red cell osmotic fragility, morphology and starch gel electrophoresis at birth allows detection and diagnosis of beta-thal heterozygosity, beta-thal homozygosity, Hb E heterozygosity, Hb E homozygosity and double heterozygosity for beta-thal and Hb E.
Subject(s)
Fetal Blood/analysis , Hemoglobin E/genetics , Hemoglobins, Abnormal/genetics , Thalassemia/genetics , Fetal Hemoglobin/analysis , Hemoglobin A/analysis , Hemoglobin E/analysis , Hemoglobins, Abnormal/analysis , Heterozygote , Homozygote , Humans , Infant, Newborn , Osmotic Fragility , Thalassemia/blood , Thalassemia/diagnosisABSTRACT
The effectiveness of the one tube method of osmotic fragility with three buffered solutions (0.32% saline, 0.36% saline, and tyrode) as a screening test for beta-thalassaemia trait was evaluated in several groups of subjects from Greece, Yugoslavia, and Thailand. The results clearly demonstrated that 0.36% saline is the most sensitive and effective solution since it could detect 96 to 100% of heterozygotes with beta-thalassaemia, compared to about 80% with both 0.32% saline and tyrode. However, 0.36% saline gave false positive results in normal subjects and was also positive in haematological disorders which influence osmotic fragility. The screening test with 0.36% saline was applied more precisely in 1371 subjects. The test was false positive in 41 (9.1%) of 455 normal subjects while of 438 confirmed heterozygotes with beta-thalassaemia it was positive in 431 (98%) and negative in only seven (2%). The test was also found to be positive in 80% of patients with iron deficiency anaemia and alpha-thalassaemia trait, in 68% of patients with Hb E trait, in 40% of patients with Hb S trait, and in 78% of heterozygotes with rare haemoglobin variants. The increased sensitivity and effectiveness of 0.36% saline in detecting beta-thalassaemia trait and other disorders influencing osmotic fragility as compared to 0.32% saline and tyrode solutions was also confirmed in a study of 384 unselected schoolchildren.
Subject(s)
Genetic Carrier Screening/methods , Thalassemia/genetics , Evaluation Studies as Topic , Female , Greece , Humans , International Cooperation , Male , Osmotic Fragility , Thailand , YugoslaviaSubject(s)
Thalassemia/genetics , Adult , Female , Fetal Hemoglobin/analysis , Fetal Hemoglobin/genetics , Genes , Genotype , Globins/biosynthesis , Globins/genetics , Hemoglobin A/analysis , Hemoglobin A/genetics , Hemoglobins/biosynthesis , Hemoglobins/genetics , Hemoglobins, Abnormal/biosynthesis , Hemoglobins, Abnormal/genetics , Heterozygote , Humans , Male , Mutation , Pedigree , Peptide Fragments , Thailand , Thalassemia/bloodABSTRACT
A healthy Thai male was found to have an abnormal hemoglobin moving faster than Hb A in starch-gel electrophoresis, in addition to the normal hemoglobin constituents. The abnormal hemoglobin constituted 28% of the whole hemoglobin. The subject was asymptomatic and had normal hematologic findings. Structural characterization revealed that the amino acid substitution was alpha 56 Lys leads to Thr. This variant has never been described previously and it is named Hb Thailand.
Subject(s)
Hemoglobins, Abnormal/isolation & purification , Lysine/metabolism , Threonine/metabolism , Acetates/pharmacology , Amino Acids , Electrophoresis, Starch Gel , Globins/isolation & purification , Humans , Male , Peptides/isolation & purification , ThailandABSTRACT
Hemoglobin Vancouver is a new abnormal hemoglobin with an amino acid substitution of the normal aspartyl residue 73 of the beta chain by a tyrosyl residue. It was discovered in a man of Chinese descent in association with beta thalassemia. It was subsequently detected in a sister in association with normal Hb A. The oxygen affinity of the abnormal hemoglobin is decreased but its subunit interaction is normal. The Bohr effect may be slightly increased. This is the fourth abnormal hemoglobin to be found with a substitution at beta73. The others are Hb C-Harlem (alpha2beta2 6Glu replaced by Val and 73 Asp replaced by Asn), Hb Korle-Bu (alpha2beta2 73Asp replaced by Asn), and Hb Mobile (alpha2beta2 73Asp replaced by Val). Although Hb Mobile was found in the present studies to have a decreased affinity for oxygen, Hbs C-Harlem and Korle-Bu have been reported to be normal. These observations of functional differences for variants of beta73 added to earlier observations of the role of the normal beta73 residue to the aggregation of sickle deoxyhemoglobin indicate that this position of the molecule may be important in intra as well as intermolecular interactions.
Subject(s)
Hemoglobins, Abnormal , Amino Acid Sequence , Aspartic Acid , Female , Hemoglobins, Abnormal/physiology , Humans , Male , Oxygen/blood , Peptide Fragments/analysis , TyrosineABSTRACT
In Thailand, two types of high Hb A2-beta-thalassemia genes: beta0-thalassemia (beta0-thal) or classical beta-thalassemia and beta+-thalassemia (beta+-thal) or mild beta-thalassemia exist. This study presents hematologic data and globin chain synthesis in peripheral blood of the genuine beta+-thal heterozygotes in comparison with those of the beta0-thal heterozygotes. Thirty individuals of Thai and Chinese extraction with the beta+-thal heterozygosity were hematologically examined. The hematologic means of hemoglobin concentration, MCV, MCH, MCHC, Hb A2 and alkali denaturation hemoglobin of the beta+-thal traits were, 11.7 g%, 67.8 mu3, 21.5 gammagamma, 32.1%, 4.94% and 1.20% respectively. These were not statistically different from those of the beta0-thal traits of our previous study(1). The globin chain synthesis in reticulocytes were performed by incorporation of 3H-Leucine for 3 hours. The mean of total radioactivity alpha/beta ratio in 11 normal controls was 1.07 +/- SD 0.03. The mean of alpha/beta ratio in 9 beta+-thal traits was 2.03 +/- SD 0.10 which was significantly different from that in 7 beta0-thal traits of 2.28 +/- SD 0.07. Our globin chain synthesis thus appears to be helpful of discriminating the beta+-thal trait from the beta0-thal trait.
Subject(s)
Hemoglobins/biosynthesis , Thalassemia/blood , Globins/biosynthesis , Heterozygote , Humans , Thalassemia/geneticsABSTRACT
Four heterozygotes for a fast alpha-chain variant in a Thai family were detected on starch gel electrophoresis during a survey study on iron deficiency anaemia in a rural area not far from Bangkok. They were healthy and had normal haematological profiles except for the presence of around 44% abnormal pigment, quantitated by cellulose acetate electrophoresis. The structural characterization of the variant by globin chain separation, peptide mapping, and amino acid analyses of the abnormal peptides indicated that lysine residue 11 (A9) of alpha-chain was replaced by glutamic acid. This mutation has not been previously described and it is proposed that it be called Haemoglobin Anantharaj.
Subject(s)
Genetic Variation , Hemoglobins, Abnormal , Amino Acid Sequence , Amino Acids/analysis , Glutamates/analysis , Heterozygote , Lysine/analysis , Peptide Fragments/analysis , ThailandABSTRACT
In the Far East two types of alpha-thalassemia genes, namely alpha-thalassemia, (alpha-thal1), and alpha-thalassemia2 (alpha-thal2) exist. Definite diagnosis of the alpha-thal1 and alpha-thal2 traits is very difficult because their hematological findings are minimally abnormal or normal. This study attempts to characterize the heterozygotes by hemoglobin chain synthesis in reticulocytes from obligatory cases of the alpha-thal1 and alpha-thal2 traits. Twelve parents of babies with hemoglobin Bart's hydrops fetalis (obligatory alpha-thal1 trait) had the mean total radioactivity alpha/beta ratio of 0.76 +/- SD 0.04, while that of 7 normal controls was 1.06 +/- SD 0.04. The alpha/beta globin chain ratios of 16 cases, who were either parents or offspring of patients with hemoglobin H disease, were found to segregate into 2 groups, i.e. 0.78 +/- SD 0.03 (10 cases) and 0.9l1 and alpha-thal2 traits respectively. The hematological data of the first group showed definite hypochromic microcytic red cells, similar to those of the parents of the hydrops. The second group had significantly higher mean corpuscular hemoglobin than the first group, compatible with alpha-thal2 trait. Our globin chain synthesis study thus appears to be capable of discriminating normal, alpha-thal1 and alpha-thal2 traits.
