Tetrahydrobiopterin treatment in phenylketonuria: A repurposing approach.

In phenylketonuria (PKU) patients, early diagnosis by neonatal screening and immediate institution of a phenylalanine-restricted diet can prevent severe intellectual impairment. Nevertheless, outcome remains suboptimal in some patients asking for additional treatment strategies. Tetrahydrobiopterin (BH ₄ ) could be one of those treatment options, as it may not only increase residual phenylalanine hydroxylase activity in BH ₄ -responsive PKU patients, but possibly also directly improves neurocognitive functioning in both BH ₄ -responsive and BH ₄ -unresponsive PKU patients. In the present review, we aim to further define the theoretical working mechanisms by which BH ₄ might directly influence neurocognitive functioning in PKU having passed the blood-brain barrier. Further research should investigate which of these mechanisms are actually involved, and should contribute to the development of an optimal BH ₄ treatment regimen to directly improve neurocognitive functioning in PKU. Such possible repurposing approach of BH ₄ treatment in PKU may improve neuropsychological outcome and mental health in both BH ₄ -responsive and BH ₄ -unresponsive PKU patients.
(© 2019 SSIEM.)