The Philadelphia variant of galactokinase

Probands with the Philadelphia variant of galactokinase (GALKP) are black people who exhibit reduced galactokinase (GALK) activity in their red blood cells (RBC), but normal activity in their white blood cells. This reduced RBC GALK was demonstrated in disrupted erythrocytes. To investigate the possibility of a missing cofactor in hemolysates from individuals with GALKP phenotype, the authors compared [1-14C]galactose oxidation by intact erythrocytes, with the direct GALK assay in disrupted erythrocytes. The rate of [1-14C]glucose oxidation was also measured in order to differentiate an impaired galactose metabolism from a defect further along the pentose phosphate pathway. For all the probands with a GALKP phenotype, diminished CO2 production from galactose was observed in the absence of impaired glucose metabolism. This allowed the authors to confirm the existence of a GALK deficiency in intact erythrocytes due to the GALKP variant. Further studies of RBC GALK catalytic properties are needed to investigate the molecular basis of this GALK deficiency. 12 refs.; 3 figs.; 2 tabs