3 MISSENSE MUTATIONS IN THE GALACTOSE-1-PHOSPHATE URIDYLTRANSFERASE GENE OF 3 FAMILIES WITH MILD GALACTOSEMIA

Classical galactosaemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is characterized by acute symptoms of hepatoc ellular dysfunction, sepsis, cataracts and failure to thrive. Galactos e limitation reverses these complications immediately, however, most o f these children have a long-term complication of verbal dyspraxia, me ntal retardation and ovarian failure. The GALT gene was cloned and sev eral mutations including the common Q188R have been reported. In this study the coding region of GALT was amplified by polymerase chain reac tion from genomic DNA of classical galactosaemic individuals and chara cterized by direct sequencing of the products. Three missense mutation s were identified in three patients with a mild galactosaemic variant: (1) replacement of threonine-138 by methionine (T138M); (2) replaceme nt of arginine by tryptophan (R259W); and (3) replacement of threonine by alanine (T350A). All three galactosaemic individuals, one girl and two boys, have varying degrees of residual GALT activity in RBC and t heir galactose-1-phosphate levels decreased much faster than in other galactosaemic patients. These missense mutations occur in regions that are not highly conserved domains. Conclusion The study of the molecul ar basis related to the pheno-type variation may indeed help to progno sticate the outcome of patients with classical galactosaemia.