Inborn error of metabolism: the classic form of galactosemia is caused by deficiency of which enzyme in the Leloir pathway of galactose utilization?

Introduction / Context:Galactosemia is an inborn error of carbohydrate metabolism leading to accumulation of toxic intermediates after milk ingestion. Identifying the defective enzyme guides diagnosis and dietary therapy.

Given Data / Assumptions:

• Clinical setting: neonatal jaundice, vomiting, hepatomegaly after lactose (milk) exposure.
• Pathway: Leloir pathway converts galactose to glucose-1-phosphate.
• We focus on the classic (most common) form.

Concept / Approach:Classic galactosemia results from GALT deficiency, blocking conversion of galactose-1-phosphate and UDP-glucose to glucose-1-phosphate and UDP-galactose, causing accumulation of galactose-1-phosphate and galactitol (via aldose reductase), with risk of cataracts and liver failure.

Step-by-Step Solution:1) Recognize key enzyme: GALT is central to Leloir pathway flux.2) Predict metabolic consequences: galactose-1-phosphate builds up; galactose is reduced to galactitol.3) Link to clinical picture: toxicity explains hepatic dysfunction and cataracts; dietary galactose restriction improves outcomes.

Verification / Alternative check:Other variants exist (galactokinase or UDP-galactose-4-epimerase deficiencies), but the classic severe neonatal presentation is most commonly due to GALT deficiency.

Why Other Options Are Wrong:Lactase deficiency: causes lactose intolerance (malabsorption), not systemic neonatal toxicity.Lactose synthetase absence: relates to lactose synthesis in mammary glands, not neonatal catabolism.“Semnase”: not an enzyme in this pathway.

Common Pitfalls:Confusing digestive brush-border enzymes (lactase) with hepatic metabolic enzymes (GALT).

Final Answer:Absence of galactose-1-phosphate uridyltransferase (GALT)