Objective: To define the mutation causing galactosemia in patients of
black American origin who have no galactose-1-phosphate uridyltransfer
ase (GALT) activity in erythrocytes but good clinical outcome. Methods
: We discovered a mutation caused by a C-->T transition at base-pair 1
158 of the GALT gene that results in a serine-to-leucine substitution
at codon 135 (S135L), We developed a method with which to screen popul
ations for its prevalence, We compared galactose-1-phosphate uridyltra
nsferase among erythrocytes,leukocytes, and transformed lymphoblasts,
as well as total body oxidation of D-(C-13)-galactose to (CO2)-C-13 am
ong three genotypes for GALT (S135L/S135L, Q188R/Q188R, and Normal/Nor
mal). Results: We found a 48% prevalence of the S135L mutation among 1
7 black American patients with classic galactosemia and a 1% prevalenc
e in a population of 50 black Americans without galactosemia, The S135
L mutation was not found in 84 white patients with G/G galactosemia no
r in 87 white control subjects without galactosemia. We found normal w
hole body oxidation of D-(C-13)-galactose by the patient homozygous fo
r S135L and various degrees of enzyme impairment among different tissu
es. Conclusions: The S135L mutation in the GALT gene is a prevalent ca
use 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 w
hen both are treated from infancy.