Haemoglobin GPhiladelphia and its interaction with haemoglobin S and alpha-thalassaemia in Nigerians.

The diagnosis of Hb SS/GPhiladelphia disease was made in four young Nigerians from separate families. Their Hb electrophoretic patterns on cellulose acetate membrane at alkaline pH were similar to those obtained in sickle-cell haemoglobin C (HbSC) disease, but their clinical features and haematological data were consistent with the diagnosis of homozygous sickle-cell disease. Family studies also revealed that they had inherited an additional alpha-chain mutant haemoglobin. In one of the families, fingerprints of the globin peptides and amino acid analysis confirmed that the mutant haemoglobin was Hb GPhiladelphia (alpha 2 68 Asn----Lys beta 2 A). The results of the whole blood solubility test for sickle-haemoglobin provided firm support for the diagnosis of homozygous sickle-cell disease and distinguished clearly Hb SS/GPhiladelphia disease from Hb SC disease and Hb AS from Hb AGPhiladelphia heterozygotes. Restriction endonuclease mapping of the globin genes of the propositus and some relatives of one of the families revealed also that they were carriers of the alpha-thalassaemia-2 gene (deletion-type). The globin gene-analysis data indicate also that the alpha GPhiladelphia and alpha-thalassaemia genes are linked closely in Nigerians.