A neonate with classic PKU is started on sapropterin (synthetic tetrahydrobiopterin). Her plasma phenylalanine normalizes without dietary restriction. Which PKU subtype does she most likely have?

• A Mild PKU with partial PAH activity preserved ✓
• B Classic PKU with severe PAH missense mutation
• C Malignant PKU due to dihydropteridine reductase (DHPR) deficiency
• D Malignant PKU due to GTP cyclohydrolase I deficiency

Explanation

Sapropterin (BH4) responsiveness occurs in mild PKU or mild hyperphenylalaninemia where residual PAH enzyme activity exists and can be pharmacologically enhanced by supraphysiologic BH4 concentrations. DHPR or GTP cyclohydrolase I deficiency are 'malignant' PKU forms where BH4 synthesis/recycling is impaired; sapropterin helps but dietary restriction and neurotransmitter precursors are also required.

Reference: Harrison's Principles of Internal Medicine, 20th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.