Globin Chain Synthesis Studies Research Articles

Hemoglobin alpha chain deficiency in black children with variable quantities of hemoglobin Bart's at birth.

Hematologic and globin chain synthesis studies have been made in 21 children, aged 2 to 6 years, many of their parents, and several normal adults and alpha-thalassemia heterozygotes. At birth, 11 children had about 5% hemoglobin (Hb) Bart's, 5 had about 2% Hb Bart's, and 5 had no trace of Hb Bart's. A significant decrease in mean corpuscular volume. (MCV) and mean corpuscular hemoglobin (MCH) values and an increase in the beta/alpha ratio was observed in the first group; microcytosis and hypochromia were absent in the children of the second group although the beta/alpha ratio was significantly increased. The alpha chain deficiency is familial. Increased alpha/alpha ratios were present in many parents although only two parents of children with 5% Hb Bart's at birth had hematologic findings suggestive of the presence of the same type of defect as observed in the children with the larger amount of Hb Bart's at birth.

The Negro Variety of Hereditary Persistence of Fetal Haemoglobin is a Mild Form of Thalassaemia

Further studies have been carried out on blood of the 15-year-old Negro male from Baltimore who was the first reported case of the homozygous state for hereditary persistence of fetal haemoglobin. His red cells contain only Hb F; Hbs A and A2 have never been detected. Over a 15-year period of follow up the red cells of this individual have shown persistent microcytosis with reduced MCH and MCV values. His whole-blood p50 value is decreased, probably because of lack of interaction between Hb F and 2,3-diphosphoglycerate. However, his haemoglobin level at the age of 15 years is lower than would be predicted from the degree of increased oxygen affinity. Globin-chain synthesis studies suggest that this is because he has a mild thalassaemia disorder with an alpha/gamma-chain production ratio of about 1.5, similar to that found in beta-thalassemia heterozygotes. Thus Negro HPFH appears to be a well-compensated form of delta beta thalassaemia.

Complex α-thalassemia-like syndrome: A cause of neonatal normoblastemia

A previously unrecognized hypochromic anemia associated with marked normoblastemia during the newborn period is reported. One male and two female siblings and a first cousin had a hypochromic anemia and marked normoblastemia (300 to 900 normoblast index per 100 white blood cells) at birth. Globin chain synthesis studies on peripheral blood of the proband at birth indicated the presence of alpha-thalassemia trait with possible reduced gamma chain synthesis. Studies of globin chain synthesis on the father, two older affected siblings of the proband, and the proband at 1.5 years of age revealed alpha-thalassemia trait. The data suggest this complex alpha-thalassemia-like condition as a new syndrome associated with marked neonatal normoblastemia.

Successful application of prenatal diagnosis in a pregnancy at risk for homozygous beta-thalassemia.

A Sicilian couple whose first child had homozygous beta-+-thalassemia requiring monthly transfusion requested prenatal diagnosis during the second pregnancy. Fully informed consent was obtained. The placenta was localized by ultra-sound at the 20th week of gestation, and was aspirated with a 20-gauge needle. Samples containing fetal red cells were obtained, and studies of globinchain synthesis showed a normal beta/gamma synthesis ratio for this gestational age. The conclusion that the child was not affected by beta-thalassemia was confirmed when an infant not affected with homozygous of heterozygous beta-thalassemia was born at term. Although more experience with this approach is necessary, this study demonstrates that prenatal diagnosis or exclusion of beta-thalassemia and sickle-cell anemia is feasible.

Gamma-beta thalassemia: a cause of hemolytic disease of the newborn.

Abstract A full-term female infant had hemolytic hypochromic anemia at birth. Blood morphology was consistent with thalassemia. Neither hemoglobin H nor hemoglobin Barts was detected. Studies of globin-chain synthesis in peripheral blood revealed a deficiency of synthesis of gamma and beta chains in relation to alpha-chain synthesis. As the infant matured, her peripheral smear morphology improved and became indistinguishable from that of her father and six other relatives who had beta thalassemia proved by measurement of globin-chain synthesis. Gamma-beta thalassemia is therefore an evanescent disease that may be severe during the normal period of dependence on gamma-chain synthesis.

Acquired hemoglobin H disease.

Abstract Although hemoglobin H disease is usually inherited, similar syndromes may be acquired. In a 73-year-old woman of British descent with a myeloproliferative syndrome characterized by striking megakaryocytic hyperplasia and thrombocytosis, we also found hemolytic anemia with hypochromia, microcytosis, marked poikilocytosis and 20 per cent hemoglobin H (beta4). Incubation with brilliant cresyl blue produced inclusions in 60 per cent of the red cells. Hematologic studies before the onset of this illness gave normal results. In vitro studies of globinchain synthesis revealed a marked decrease of alpha-chain production similar to that found in hereditary hemoglobin H disease. The alpha/beta ratio of radioactivities was 0.13, demonstrating a severe imbalance of globin synthesis. Studies of the patient's two children gave normal results. Hematologic and globin synthesis in this acquired disorder is similar to those of its hereditary counterpart.