An infant with phenylketonuria (PKU) detected on newborn screening is started on a phenylalanine-restricted diet. If untreated, the primary mechanism of neurological damage in PKU is:
- A Direct hepatotoxicity from phenylpyruvate buildup
- B Accumulation of DOPA causing dopaminergic excess
- C Accumulation of phenylalanine competing with other large neutral amino acids for transport across the blood-brain barrier, causing reduced tyrosine, tryptophan, and neurotransmitter deficiency ✓
- D Deficiency of phenylalanine causing reduced protein synthesis
Correct answer: C. Accumulation of phenylalanine competing with other large neutral amino acids for transport across the blood-brain barrier, causing reduced tyrosine, tryptophan, and neurotransmitter deficiency
Explanation
In PKU, deficiency of phenylalanine hydroxylase causes phenylalanine accumulation. High phenylalanine competitively inhibits the large neutral amino acid transporter (LAT1) at the BBB, reducing brain uptake of other large neutral amino acids (tyrosine, tryptophan, branched-chain AAs). This causes deficiency of dopamine, serotonin, and myelin synthesis precursors in the developing brain, resulting in intellectual disability, microcephaly, and behavioral abnormalities. It is the transport competition, not just high phenylalanine itself, that is the proximate mechanism of brain injury.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.