Molecular Genetics of Galactosaemia

Galactosaemia is a relatively rare, genetic disease that commonly manifests with cataracts in childhood. More severe forms result in significant developmental abnormalities resulting in physical and cognitive disabilities. Three genes are affected: galactose 1‐phosphate uridylyltransferase (GALT; type I galactosaemia), galactokinase (GALK1; type II) and UDP‐galactose 4'‐epimerase (GALE; type III). Clinical outcomes vary widely in severity and depend on the gene affected, the precise mutation(s) present and the patient's environment. The disease can be diagnosed by altered metabolite levels, reduced enzyme activity and sequencing of the affected gene. In many cases, mutations in one of these three genes result in a protein that is unstable and/or misfolded with consequent reduction in enzymatic activity. Understanding how loss of activity of these enzymes results in the disease phenotypes is a key priority in current research.