The Philadelphia variant of galactokinase

We have previously reported the existence of a polymorphism that causes black populations to have lower mean RBC galactokinase activity than comparable white populations. We have designated this allele the Philadelphia variant, GALKP, and have suggested that it is common in blacks and rare in whites. GALKP individuals have normal WBC GALK activity, in contrast to the half normal WBC GALK activities of heterozygotes for the allele (GALKG) that causes the galactokinase-deficient form of galactosemia. In one family, we have presented evidence for the existence of two sisters heterozygous for both GALKG and GALKP alleles. These individuals have 50% normal WBC GALK activity and less than 50% normal red cell activity. The latter finding indicates that the two variant GALK alleles additively affect RBC activity. The WBC results suggest that the low activity of GALK in RBC of individuals with the GALKP allele is due to its relative instability. We could obtain no evidence for such instability from studies of high reticulocyte bloods or RBC fractionation. Furthermore, we could not demonstrate that the GALK in WBC from GALKP individuals has altered electrophoretic migration.