A 3-year-old child with fair skin, eczema, and musty-smelling urine is brought for evaluation of intellectual disability and hyperactivity. Serum phenylalanine is 28 mg/dL (reference < 2 mg/dL). Which enzyme deficiency is responsible, and what is the direct metabolic consequence?
- A Phenylalanine hydroxylase deficiency, causing accumulation of phenylalanine and its transamination products such as phenylpyruvate ✓
- B Tyrosinase deficiency, causing failure of melanin synthesis from tyrosine
- C Homogentisate oxidase deficiency, causing accumulation of homogentisic acid in tissues
- D Fumarylacetoacetate hydrolase deficiency, causing liver and kidney damage from succinylacetone accumulation
Correct answer: A. Phenylalanine hydroxylase deficiency, causing accumulation of phenylalanine and its transamination products such as phenylpyruvate
Explanation
Classical PKU results from phenylalanine hydroxylase (PAH) deficiency, impairing conversion of phenylalanine to tyrosine. Accumulated phenylalanine is shunted to alternative pathways producing phenylpyruvate (by transamination), phenylacetate, and phenyllactate. These compounds are excreted in urine (musty/mousy odor) and inhibit myelin synthesis, causing neurological damage. Tyrosine becomes conditionally essential.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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