Elevated Fetal Hemoglobin Research Articles

Sociocultural and Ethnohistorical Influences on Genetic Diversity in Liberia

In the Republic of Liberia where falciparum malaria remains highly endemic, four phenotypes reported to provide an innate resistance to malaria are nonuniformly distributed among the country's geographical regions and indigenous ethnic groups. Significant regional variation is observed in the prevalence of sickle cell trait and nonsignificant but ostensible variation is seen in the distributions of beta thalassemia trait, elevated fetal hemoglobin, and intermediate red cell G6PD deficiency. It appears that particular cultural and historical factors may exert important influences on genetic diversity in this area of West Africa. A study of the regional and ethnic variation in these four phenotypes among 961 indigenous children and mothers suggests that the sociocultural variables most likely to increase assortive mating and nonrandom gene flow include (1) membership in the Poro and Sande traditional initiation societies, (2) linguistic affiliation, (3) dietary staple, and (4) religious preference. Ethnohistorical events most likely to explain the origins of this diversity are discussed in light of the population's pre-Liberian origins, time and direction of major migrations, nature of interethnic hostilities, evidence of assimilation, and enslavement patterns.

Acetylation of human fetal hemoglobin occurs throughout erythroid cell maturation

The biosynthesis of human acetylated fetal hemoglobin (Hb F 1) has been examined by incubating the following cell types with [ 3H]leucine: (a) burst-forming unit erythroid cells cultured from umbilical cord mononuclear cells, (b) infant bone marrow, (c) umbilical cord blood, and (d) peripheral blood cells from adults with elevated fetal hemoglobin. Newly synthesized Hb F 1 was 18–20% that of Hb F 0 in burst-forming unit erythroid cells which were immature, mature, or in an intermediate state of development. In infant marrow and in infant and adult peripheral blood the extant Hb F 1 comprised 10.8 ± 1.8 of the total Hb F. In marrow cells the specific radioactivity (cpm/mg) of Hb F 1 was 1.4–2.0-times greater than that of Hb F 0. In peripheral blood cells these ratios were slightly greater. [ 3H]Leucine-labeled infant bone marrow, umbilical cord blood, and adult peripheral blood cells were subjected to density gradient ultracentrifugation. The ratio of specific radioactivity for Hb F 1/Hb F 0 increased from 1.0–1.8 in the lightest cell zone to 5.2–9.0 in the more dense cells. Thus the biosynthesis of Hb F 1 is enhanced in cells which are more mature than those responsible for the bulk of hemoglobin synthesis, and the acetylation of Hb F provides a marker of erythroid cell maturation.

Paroxysmal Nocturnal Hemoglobinuria with Elevated Fetal Hemoglobin

Abstract A persistent elevation of the fetal hemoglobin (Hgb F) level (5%-15%) was observed in a 22-yr-old white male with paroxysmal nocturnal hemoglobinuria (PNH). Acid treatment of the peripheral smear (Betke-Kleihauer technique) demonstrated a heterogeneous distribution of Hgb F in the red cells. As expected, the lowest acetylcholinesterase activity and the most hemolysis after acid stress were found in the low-density, reticulocyte-rich cell fraction. In contrast, the highest Hgb F levels were found in the high-density, reticulocyte-poor fraction. Further evidence for the segregation of these two abnormalties was obtained from the observation that less Hgb F was present in the hemolysate obtained after acid lysis than was present in the mixed blood sample or the remaining nonhemolyzed red cells.

Double Heterozygous ßd-Thalassemia in Negroes

The biochemical defect in thalassemia is thought to consist of a diminished capacity of the erythropoietic cells to synthesize one of the polypeptide chains of hemoglobin. Thus, the common variants of this disease have been designated as αand β-thalassemia. β-Thalassemia is usually associated with a twofold increased proportion of hemoglobin A2and a slight elevation of fetal hemoglobin (hemoglobin F) in hemolysates, but many families have been described in which the hemoglobin abnormality is characterized by low or normal levels of hemoglobin A2and high concentrations of hemoglobin F (10% to 30%). This variant of the disease has been designated as F-thalassemia or βδ-thalassemia since the synthesis of both β- and δ-chains appears to be impaired. The distribution of hemoglobin F in the erythrocyte population is uneven in contrast to the hereditary persistence of fetal hemoglobin (HPFH) in which all erythrocytes appear to have the same concentration of hemoglobin

F-thalassemia: A study of thirty-one families with simple heterozygotes and combinations of F-thalassemia with A 2-thalassemia

Phenotypes of F-thalassemia are described, as revealed by a study of sixty-eight simple heterozygotes and twenty-one combinations with A 2-thalassemia. Simple heterozygotes present with typical hematologic stigmata of the thalassemia trait, elevated fetal hemoglobin levels and normal hemoglobin A 2. Double heterozygotes for F-thalassemia and A 2-thalassemia display heterogeneity in their clinical and hematologic picture, but when compared to homozygotes for A 2-thalassemia they are found to have milder clinical manifestations, less anemia and usually no transfusion requirement. Absence of hemoglobin A was observed in more than one third of double heterozygotes. Mean hemoglobin A 2 in simple heterozygotes was 50 per cent lower than in those with A 2-thalassemia trait. Elevation of fetal hemoglobin levels was observed in all but one simple heterozygote and was transmitted in a dominant pattern of inheritance. High intrafamilial similarities in the levels of hemoglobin F were documented. The data are analyzed in relation to the information on F-thalassemia thus far available. The over-all picture is that of a mutation causing defective red cell hemoglobinization, simultaneous suppression of β and δ hemoglobin chain synthesis in cis position and hereditarily determined elevation of fetal hemoglobin levels. The proposed molecular mechanisms are discussed. It is concluded that current hypotheses as to the pathogenesis of thalassemias and prevailing concepts of the regulation of hemoglobin genes cannot account for the findings in F-thalassemia.

The thalassaemia syndromes. VI. Two subtypes of sickle cell-beta thalassaemia disease: (a) normocytic type of sickle cell-beta thalassaemia disease (b) microcytic type of sickle cell-beta thalassaemia disease.

Two cases of thalassaemia minor with slightly elevated fetal haemoglobin are described. The patients resembled in every respect to intermediate type of Cooley's anaemia or thalassaemia minor with large amount of fetal haemoglobin. But there was only one difference between them, namely, the amount of fetal haemoglobin was less than 5%. The possible genetic explanation for this unusual observation is discussed.

The occurrence of the i antigenand elevated fetal hemoglobin in hemopoietic disorders

The occurrence of the i antigenand elevated fetal hemoglobin in hemopoietic disorders

THE THALASSAEMIA SYNDROMES. 3. A SEVERE FORM OF THALASSAEMIA MINOR WITH SLIGHTLY ELEVATED FETAL HAEMOGLOBIN. STUDY OF TWO FAMILIES.

Two cases of thalassaemia minor with slightly elevated fetal haemoglobin are described. The patients resembled in every respect to intermediate type of Cooley's anaemia or thalassaemia minor with large amount of fetal haemoglobin. But there was only one difference between them, namely, the amount of fetal haemoglobin was less than 5%. The possible genetic explanation for this unusual observation is discussed.