Which of the following clinical laboratory observations is suggestive of Hanup disease?
**Core Concept**
Hanup disease, also known as **tryptophan metabolism disorder**, is a rare autosomal recessive condition characterized by impaired tryptophan catabolism due to deficiency of the enzyme **tryptophan 2,3-dioxygenase**. This leads to accumulation of tryptophan and its metabolites, particularly **indole derivatives**, in the gut and feces.
**Why the Correct Answer is Right**
In Hanup disease, defective tryptophan metabolism results in increased conversion of tryptophan to **indole** and its derivatives, which are excreted in high amounts in feces. This leads to **elevated fecal levels of tryptophan and indole compounds**, which can be detected in stool tests. The condition is distinct from other amino acid disorders like phenylketonuria or urea cycle defects, as it involves the **tryptophan–kynurenine pathway** and not the phenylalanine or citrulline pathways.
**Why Each Wrong Option is Incorrect**
Option A: Burnt sugar smell in urine is characteristic of **maple syrup urine disease**, not Hanup disease.
Option B: High plasma phenylalanine is seen in **phenylketonuria**, not Hanup disease.
Option C: Extremely high citrulline in urine is associated with **urea cycle disorders** like citrullinemia or urea cycle defects, not tryptophan metabolism.
**Clinical Pearl / High-Yield Fact**
Remember: **Hanup disease = elevated fecal tryptophan and indole**. Always check fecal metabolites when suspecting tryptophan pathway disorders. This is a rare but important diagnostic clue in metabolic screening.
✓ Correct Answer: D. High fecal levels of tryptophan and indole derivatives