Which enzyme deficiency causes classic galactosemia?

• A. Galactose-1-phosphate uridyltransferase (GALT)
• B. Galactokinase
• C. UDP-glucose 4-epimerase
• D. Aldose reductase

Answer: (A)

Classic galactosemia occurs when galactose-1-phosphate uridyltransferase is deficient, a key step in the Leloir pathway that normally transfers UDP from UDP-glucose to galactose-1-phosphate to form UDP-galactose and glucose-1-phosphate. Without this enzymatic activity, galactose-1-phosphate and galactose build up, causing liver-related symptoms like jaundice, hepatomegaly, vomiting, and failure to thrive in newborns, and potentially severe long‑term complications if not treated.

This is the best answer because the deficiency of this specific enzyme directly blocks the primary galactose metabolism reaction responsible for the classic, neonatal presentation. If galactokinase were deficient, the issue would be mainly cataracts from galactitol accumulation, not the full neonatal syndrome. UDP-glucose 4-epimerase deficiency can cause galactosemia-like problems but with a different pattern and variability. Aldose reductase is involved later in converting galactose to galactitol in the lens, contributing to cataracts, but it is not the cause of classic galactosemia itself.