Galactosemia is caused by metabolic disturbances at various stages of galactose metabolism, including deficiencies in enzymes involved in the Leloir pathway (GALT, GALK1, and GALE).
Deficiencies in three of the enzymes of the Leloir pathway, namely, GALT, GALK1, or GALE, are characterized as type I, II, and III galactosemia, respectively.
The metastability of human UDP-galactose 4'-epimerase (GALE) is increased by variants associated with type III galactosemia but decreased by substrate and cofactor binding.
Therefore, it is suggested that reduced catalytic efficiency and increased proteolytic susceptibility of GALE are causative factors in type III galactosemia.
Cloning and characterization of all three human galactose-metabolic genes (GALK, GALT and GALE) has led to the identification of a number of mutations which are generally of the missense type in patients with galactosemia, an inborn error of metabolism.
This report represents the first characterization of specific mutations in a GALE-deficient patient in conjunction with biochemical and clinical phenotype, and facilitates further studies of the GALE enzyme and its role in the different clinical forms of epimerase-deficiency galactosaemia.