Hb S, Hb G-PHILADELPHIA AND α-THALASSEMIA-2 IN A BLACK FAMILY

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Abstract
Summary: A Black family is described in which Hb S, Hb G-Philadelphia and α-thal-assemia-2 determinants occurred in different combinations. The propositus was a healthy fullterm neonate who had 46% Hb G-Philadelphia and about 5% Hb Bart's in cord blood together with a relative microcytosis (MCV = 85 f1***) and hypochromia (MCH = 28 pg). This is consistent with a diagnosis 6f Hb G-Philadelphia trait in association with a homozyqous α-thalassemia-2 {a°α/a°αG βA/βA). The mother and another son also had Hb G-Ph1ladelphia in association with Hb S trait but with 373 Hb G-Philadelphia and with 391 Hb S. Hematological and biosynthetic studies confirm the assignment of the αα/αDα; βA/βAgenotype in both and that of the αα/αDα; βA/βA genotype in the father. Despite this evidence for a moderate α chain deficiency in the propositus, the biosynthetic α/non-α value in the neonatal period was a high 1.2. Similar values were observed in 8 control cord blood samples if the incubation was not delayed longer than 3 hours after collection (α /non-α = 1.28 ± 0.14). When the propositus was studied again, but at six months of age, the proportion of Hb G-Philadelphia in peripheral blood was unchanged, a marked microcytosis and hypochromia were observed, and a distinct deficiency of α chain synthesis (α /non-α = 0.56) was present. Speculation: The occurrence of a decreased number of active α chain genes due to the inheritance of α-thalassemia-2 determinants causes the proportion of the α chain variant Hb G-Philadelphia to Increase and the proportion of the β chain variant Hb S to decrease. Thus, the levels of these two abnormal hemoglobins help to define the number of active α chain genes and the occurrence of α-thalassemia. Despite the existence of a moderate α chain deficiency, the failure to detect any decreased in vitro synthesis of α chains in this neonate as well as the finding of excessive In vitro α chain synthesis in normal neonates suggest that during the transition from fetal to adult type of erythropoiesis, the synthesis of γ chains may decline more rapidly than that of α chains before the synthesis of β chains is established.