Evidence for alternate galactose oxidation in a patient with deletion of the galactose-1-phosphate uridyltransferase gene.

The persistent, dietary-independent elevation of galactose metabolites in patients with galactose-1-phosphate uridyltransferase (GALT) deficiency is probably secondary to de novo synthesis of galactose. Relatively constant steady-state levels of galactose metabolites in patients also suggest that non-GALT metabolic pathways must function to dispose of the galactose synthesized each day. The discovery of a patient with a rare deletion of the GALT gene provided a unique opportunity to examine the availability of any alternate galactose oxidative capacity both in vivo and in vitro. Utilizing genomic DNA from the patient, Southern blot data demonstrated that 10 of the 11 GALT exons were homozygously deleted. By measurement of 13CO2 in expired air for up to 24 h after an oral bolus of [1-13C]galactose, it was demonstrated that 17% of the galactose was metabolized, a value comparable to the 3-h elimination rate in a control subject. Furthermore, lymphoblasts prepared from the patient could also convert [1-14C]galactose to 14CO2. This unique study provides the first unambiguous evidence that another pathway exists in man that can be responsible for galactose disposal. Further knowledge of this alternate galactose oxidative route and its regulation may aid in formulating new strategies for the treatment of galactosemia. Copyright 2001 Academic Press.