A 2-week-old neonate born to consanguineous parents presents with vomiting, jaundice, hepatomegaly, and failure to thrive after initiation of milk feeding. Laboratory investigations show elevated galactose-1-phosphate levels and reduced enzyme activity. Newborn screening confirms deficiency of the enzyme marked **B** in the galactose metabolism pathway diagram. Which of the following is the most appropriate long-term management for this patient?

Explanation

## Why "Lifelong galactose and lactose-free diet with avoidance of milk and dairy products" is right Classic galactosemia results from autosomal recessive deficiency of galactose-1-phosphate uridyltransferase (GALT), the enzyme marked **B**. When GALT is deficient, galactose-1-phosphate accumulates and causes severe neonatal toxicity: hepatomegaly, jaundice, vomiting, failure to thrive, E. coli sepsis (due to neutrophil dysfunction), and cataracts from galactitol accumulation. The only effective treatment is lifelong dietary avoidance of galactose and lactose (the disaccharide that yields galactose upon hydrolysis). This prevents substrate accumulation and halts disease progression. Early diagnosis via newborn screening and prompt dietary intervention prevent mental retardation, cirrhosis, and death. (Harper 32e Ch 20; Nelson 21e) ## Why each distractor is wrong - **Supplementation with UDP-galactose to bypass the enzymatic defect**: UDP-galactose supplementation cannot bypass the block at GALT; it would only worsen galactose-1-phosphate accumulation and is not used in management. The defect is irreversible enzymatically. - **Dietary restriction of glucose while allowing lactose-containing foods**: Lactose contains galactose and must be strictly avoided. Restricting glucose alone does not address the galactose burden and would allow continued substrate accumulation and organ damage. - **Enzyme replacement therapy with recombinant GALT protein**: Enzyme replacement therapy is not standard for galactosemia. The blood–brain barrier and tissue penetration issues make this impractical. Dietary management is the gold standard and only proven effective intervention. **High-Yield:** Classic galactosemia = GALT deficiency → neonatal crisis (sepsis, cataracts, liver disease) → lifelong lactose-free diet is curative; galactokinase deficiency = only cataracts (benign). [cite: Harper 32e Ch 20; Nelson 21e]