Classic galactosemia results from deficiency of which enzyme?

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

Answer: (A)

Classic galactosemia occurs when the enzyme that handles galactose-1-phosphate in the Leloir pathway is missing. After a baby begins feeding on lactose, galactose is first converted to galactose-1-phosphate by galactokinase. The next step normally uses galactose-1-phosphate and UDP-glucose to form glucose-1-phosphate and UDP-galactose, a reaction catalyzed by galactose-1-phosphate uridyltransferase. When this enzyme is deficient, galactose-1-phosphate and related metabolites build up, causing toxicity especially in the liver, brain, and eyes, and leading to symptoms like liver dysfunction, feeding problems, jaundice, and later cataracts. Treatment focuses on removing lactose from the diet to prevent further accumulation.

Other enzymes listed correspond to different disorders in the same pathway: galactokinase deficiency mainly causes galactose accumulation with early cataracts but not the full classic galactosemia picture; UDP-galactose 4'-epimerase deficiency can produce a broader, variable set of symptoms; and galactose mutarotase deficiency is rare and not the typical cause.