A newborn with undetected phenylketonuria (PKU) is breast-fed. By 3 months, the mother notices reduced alertness and poor feeding. Urinalysis shows phenylpyruvate. The enzyme deficiency most commonly responsible in classic PKU is:

• A Phenylalanine transaminase
• B Dihydropteridine reductase (DHPR)
• C GTP cyclohydrolase I
• D Phenylalanine hydroxylase (PAH) ✓

Explanation

Classic PKU (>98% of cases) results from deficiency of phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine using tetrahydrobiopterin (BH4) as cofactor. Accumulated phenylalanine is transaminated to phenylpyruvate (a phenylketone), detected in urine. Malignant hyperphenylalaninemia due to DHPR or BH4-synthetic defects (GTP cyclohydrolase I) is rarer and responds poorly to dietary restriction alone because BH4 is also required for tyrosine and tryptophan hydroxylases (neurotransmitter synthesis).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.