Galt phenotyping with galactosaemia screening

Abstract

Galactosaemia is an autosomal recessive disorder arising from deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). Enzyme activities determined by the 3 alleles, N, D and ‘G’, are 100%, 50% and approximately 0%, respectively. Expected activity levels for the genotypes ND, DD, NG and DG are 75%, 50%, 50% and 25% respectively. Alleles N and D are electrophoretically distinguishable and corresponding allele frequencies from 69 Adelaide newborns are .92 and .08. In the absence of phenotyping, confusion may arise in the interpretation of quantitative results when both D and G segregate within a family. New born propositi are routinely detected by mass screening on the basis of low GALT activity from bloodspots. Subsequently, those tests found deficient on screen have activity quantitated, and are phenotyped by electrophoresis of haemolysates. Where activity is low, detection of a D band in the propositus differentiates the classical (GG) galactosaemic infant from the DG variant type with 25%i normal activity. Phenotypic studies of parents confirms this. Galactosaemia is an autosomal recessive disorder arising from deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT). Enzyme activities determined by the 3 alleles, N, D and ‘G’, are 100%, 50% and approximately 0%, respectively. Expected activity levels for the genotypes ND, DD, NG and DG are 75%, 50%, 50% and 25% respectively. Alleles N and D are electrophoretically distinguishable and corresponding allele frequencies from 69 Adelaide newborns are .92 and .08. In the absence of phenotyping, confusion may arise in the interpretation of quantitative results when both D and G segregate within a family. New born propositi are routinely detected by mass screening on the basis of low GALT activity from bloodspots. Subsequently, those tests found deficient on screen have activity quantitated, and are phenotyped by electrophoresis of haemolysates. Where activity is low, detection of a D band in the propositus differentiates the classical (GG) galactosaemic infant from the DG variant type with 25%i normal activity. Phenotypic studies of parents confirms this.