Hemoglobin α Chain Deficiency in Black Children with Variable Quantities of Hemoglobin Bart's at Birth

Abstract

Summary: 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 α-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 β/α ratio was observed in the first group; microcytosis and hypochromia were absent in the children of the second group although the β/α ratio was significantly increased. The α chain deficiency is familial. Increased α/α 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. Speculation: It is postulated that the absence or presence of duplicated Hb_α structural genes is the underlying mechanism for the variable α chain deficiency in black infants. Children with about 5% Hb Bart's at birth have the genotype -α/- α or, rarely, the –/α α genotype; when only two Hb_α structural loci instead of four are active, a modest deficiency in a chain production will be the result. The presence of the -α/αα genotype could be predicted from the small amounts of Hb Bart's at birth and from data of the hemoglobin synthesis analyses in older children and adults; the -α/α genotype however, is also suggested from data obtained by MCH and MCV determinations. It is concluded that although the -α/α genotype always produces Hb Bart's at birth in moderate amounts, the -α/αα genotype may or may not. The rarity of the - -/αα genotype in this population is responsible for the absence of the Hb Bart's hydrops fetalis syndrome.