1. a) Sapropterin (BH4)

• Synthetic tetrahydrobiopterin, a cofactor of phenylalanine hydroxylase.
• Effective only in BH4-responsive PKU (approximately 20–50% of patients).
• Lowers phenylalanine levels and often allows a more liberal diet.

1. b) Pegvaliase

• Enzyme replacement therapy (phenylalanine ammonia lyase).
• For adults with PKU that is difficult to control.
• Breaks down phenylalanine independently of the defective enzyme.
• High efficacy, but associated with significant side effects → close monitoring is required.

3. Regular Monitoring

• Blood phenylalanine measurements (frequent in infants, less frequent later).
• Target ranges vary by age and guideline (typically approx. 120–360 µmol/L).
• Dietary adjustments based on test results.

4. Special Situations

Pregnancy (Maternal PKU)

• Very strict metabolic control before and during pregnancy, as elevated phenylalanine levels are teratogenic.
• Prevention of congenital malformations, microcephaly, and developmental disorders in the fetus.

5. Psychosocial and Multidisciplinary Care

• Management by specialized metabolic centers.
• Nutritional counseling, psychosocial support, and transition to adult care.
• Promotion of treatment adherence, particularly in adolescents and adults.

Summary