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A prevalent mutation for galactosemia among black Americans
K Lai1, S D Langley, R H Singh
1Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
The Journal of Pediatrics
|January 1, 1996
Summary
A specific mutation, S135L, is a common cause of galactosemia in Black Americans, leading to good clinical outcomes. This finding helps understand genetic variations in galactosemia.
Area of Science:
- Genetics
- Biochemistry
- Metabolic Disorders
Background:
- Galactosemia is a genetic disorder affecting galactose metabolism.
- Classic galactosemia is caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene.
- Understanding genetic variations is crucial for predicting clinical outcomes.
Purpose of the Study:
- To identify the genetic mutation responsible for galactosemia in Black American patients with no detectable GALT activity but favorable clinical prognoses.
- To investigate the prevalence of this mutation in different populations.
Main Methods:
- Discovered a C-->T transition at base-pair 1158 of the GALT gene, resulting in a serine-to-leucine substitution at codon 135 (S135L).
- Developed a population screening method for the S135L mutation.
- Compared GALT activity across tissues (erythrocytes, leukocytes, lymphoblasts) and whole-body D-(13C)-galactose oxidation in individuals with different GALT genotypes (S135L/S135L, Q188R/Q188R, Normal/Normal).
Main Results:
- Identified a 48% prevalence of the S135L mutation in 17 Black American patients with classic galactosemia.
- Found a 1% prevalence of S135L in 50 Black American control subjects.
- Observed normal whole-body D-(13C)-galactose oxidation in S135L homozygous patients, with varying enzyme impairment across tissues; the mutation was absent in white patients and controls.
Conclusions:
- The S135L mutation is a frequent cause of galactosemia in Black patients.
- Tissue-specific variations in GALT activity for S135L homozygotes may contribute to better clinical outcomes compared to Q188R homozygotes when treated early.