A prevalent mutation for galactosemia among black Americans

Objective: To define the mutation causing galactosemia in patients of black American origin who have no galactose-1-phosphate uridyltransferase (GALT) activity in erythrocytes but good clinical outcome. Methods: We discovered a mutation caused by a C-->T transition at base-pair 1158 of the GALT gene that results in a serine-to-leucine substitution at codon 135 (S135L), We developed a method with which to screen populations for its prevalence, We compared galactose-1-phosphate uridyltransferase among erythrocytes,leukocytes, and transformed lymphoblasts, as well as total body oxidation of D-(C-13)-galactose to (CO2)-C-13 among three genotypes for GALT (S135L/S135L, Q188R/Q188R, and Normal/Normal). Results: We found a 48% prevalence of the S135L mutation among 17 black American patients with classic galactosemia and a 1% prevalence in a population of 50 black Americans without galactosemia, The S135L mutation was not found in 84 white patients with G/G galactosemia nor in 87 white control subjects without galactosemia. We found normal whole body oxidation of D-(C-13)-galactose by the patient homozygous for S135L and various degrees of enzyme impairment among different tissues. Conclusions: The S135L mutation in the GALT gene is a prevalent cause of galactosemia among black patients, Because GALT activity varies in different tissues of patients homozygous for S135L, they may have a better clinical outcome than patients who are homozygous for Q188R when both are treated from infancy.