Phenotype-Genotype Discrepancy Due to a 5.5-kb Deletion in the GALT Gene

Classical galactosemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT). More than 200 mutations have been described in the GALT gene. A 5.5-kb GALT deletion, first described in patients of Ashkenazi Jewish ancestry, may lead either to an erroneous genotype assignment of classical galactosemia or to discrepancies with parental genotypes and the expected biochemical phenotype. The presence of the 5.5-kb deletion was examined in 27 Mexican nonrelated families with at least one child with reduced GALT activity in erythrocytes and it was detected in the 5.5% (n=3) of the 54 alleles tested. The first molecular studies in three of our families showed that the genotypes of the parents were inconsistent with those of their children, which were considered initially as homozygous p.N314D-Duarte 2, but after analyzing for the presence of the 5.5-kb deletion, were reassigned as compound heterozygotes [5.5-kb deletion]+[p.N314D-Duarte 2]. Identification of the 5.5-kb deletion in Mexican patients suggests that this mutation might not be exclusive to a given ethnic group and should be tested in other populations, especially when there is a discrepancy between the genotypes of patients and parents or by incongruence between biochemical phenotype and GALT genotype. Establishing a genotype–phenotype correlation for the 5.5-kb GALT deletion and determining the appropriate management will require additional studies in patients with a G/G genotype bearing the 5.5-kb GALT deletion.