Effect of tetrahydrobiopterin on Phe/Tyr ratios and variation in Phe levels in tetrahydrobiopterin responsive PKU patients

BH4 responsive patients have smaller variations in blood Phe levels and tighter Phe/Tyr ratios than non-BH4 responsive patients, particularly at high blood Phe levels. If decreased fluctuations in Phe levels and a decreased Phe/Tyr ratio are indeed neuro-protective, then BH4 responsiveness is advantageous over diet alone in PKU. Neuropsychological testing in patients who have been treated with BH4 long term may be able to ascertain the clinical benefit of these biochemical findings.