Classic galactosemia results from deficiency of which enzyme?

• A. Lactase
• B. Galactose-1-phosphate uridyltransferase (GALT)
• C. Galactokinase
• D. UDP-galactose 4'-epimerase

Answer: (B)

The main concept is how a block in the galactose metabolism pathway causes disease. Classic galactosemia occurs when the enzyme that transfers UDP from UDP-glucose to galactose-1-phosphate is missing. This enzyme, galactose-1-phosphate uridyltransferase, normally converts galactose-1-phosphate and UDP-glucose into glucose-1-phosphate and UDP-galactose. Without this step, galactose-1-phosphate and related toxic metabolites build up, especially after milk exposure in newborns, leading to the illness seen in classic galactosemia.

Other defects in the pathway cause different pictures but don’t produce the same classic presentation. Deficiency of galactokinase blocks the first phosphorylation step and mainly causes cataracts. Deficiency of UDP-galactose 4'-epimerase leads to a milder or more variable form. Lactase deficiency is a gut enzyme issue that causes lactose intolerance, not a problem with cellular galactose metabolism.