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-(13C)-galactose to 13CO2 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-(13C)-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.
Lai
K
K
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Langley
S D
SD
Singh
R H
RH
Dembure
P P
PP
Hjelm
L N
LN
Elsas
L J
LJ
D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005693:Galactosemias / Q000178:diet therapy / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D011159:Population Surveillance; D015995:Prevalence; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000235:genetics*; D001741:Black or African American
D005694:UTP-Hexose-1-Phosphate Uridylyltransferase