A musty odor in an infant's urine at about one week of age is most suggestive of which metabolic disorder?

• A. Maple syrup urine disease
• B. Isovaleric acidemia
• C. Phenylketonuria
• D. Homocystinuria

Answer: (C)

A musty odor in a newborn’s urine is a classic clue for phenylketonuria. This occurs because a defect in phenylalanine metabolism leads to the buildup of phenylalanine and a metabolite called phenylacetate, which gives that distinctive musty, mouse-like smell in the urine of affected infants. It helps distinguish PKU from other metabolic disorders that can present early. For example, maple syrup urine disease causes a sweet, maple syrup–like odor from accumulation of branched-chain ketoacids; isovaleric acidemia produces a sweaty feet odor due to isovaleric acid buildup; and homocystinuria typically presents with signs such as lens subluxation and thromboembolism rather than a characteristic urine odor. Recognizing this odor cue prompts confirmatory testing and urgent management. Management focuses on a phenylalanine-restricted diet with adequate tyrosine, and early treatment prevents intellectual disability; newborn screening routinely detects PKU for timely intervention.