A 1-year-old child, on a routine well child visit, was discovered to have cataract formation in both eyes. Blood test demonstrated elevated galactose and galactitol levels. In order to determine which enzyme might be defective in the child, which intracellular metabolite should be measured?

The child has a form of galactosemia. The elevated galactose enters the lens of the eye, is reduced to galactitol, and is trapped. The difference in osmotic pressure across the lens of the eye leads to cataract formation. Galactose is phosphorylated by galactokinase to galactose-1-phosphate, which reacts with UDP-glucose in a reaction catalyzed by galactose-1-phosphate uridylyl transferase to form UDP-galactose and glucose-1-phosphate. An epimerase converts UDP-galactose to UDP-glucose. Deficiencies in either galactokinase (nonclassical) or galactose-1-phosphate uridylyl transferase (classical) result in galactosemia, with elevated levels of galactose and galactitol (reduced galactose) in the blood. An intracellular measurement of galactose-1-phosphate can allow a definitive diagnosis to be obtained (such levels would be nonexistent if the defect were in galactokinase, and the levels would be greatly elevated if the galactose-1-phosphate uridylyl transferase enzyme were defective).