ABSTRACT
BACKGROUND: Classical galactosemia is an autosomal recessive inherited metabolic disorder caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. GALT enzyme deficiency leads to the accumulation of galactose-1-phosphate in various organs, causing hepatic, renal and cerebral impairment. Over 300 mutations have been reported in the GALT gene. The aim of this study was to describe molecular characterization of GALT gene in Argentinian patients with decreased GALT activity, and to correlate molecular results with enzyme activity. METHODS: 37 patients with enzyme activity below 6.3 µmol/h/g Hb (35% of normal value) were included. GALT activity was measured on red blood cells. DNA was extracted from peripheral blood. p.Gln188Arg mutation was studied by PCR-RFLP and, on samples negative or heterozygous, GALT gene was sequenced. In vivo splicing analysis of the GALT gene was performed on RNA extracted from leukocytes of one patient. RESULTS: 14 different sequence variations were identified among 72 unrelated alleles. The two most common disease-causing mutations were p.Gln188Arg (24/72) and p.Lys285Asn (9/72). Three novel mutations were detected. One of them, c.688G>A, caused partial skipping of exon 9 of the GALT gene. Enzyme activity correlated with GALT genotype in 36 of the 37 patients. CONCLUSION: This is the first report of sequence variations in the GALT gene in the Argentinian population. This study highlights the contribution of the molecular analysis to the diagnosis of Galactosemia and reveals c.688G>A as a novel Duarte-like variant, with a high prevalence in our population.
