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Tetrahydrobiopterin treatment in phenylketonuria: A repurposing approach

Evers, R. A. F., van Vliet, D. & van Spronsen, F. J., Mar-2020, In : Journal of Inherited Metabolic Disease. 43, 2, p. 189-199 11 p.

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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 (BH4) could be one of those treatment options, as it may not only increase residual phenylalanine hydroxylase activity in BH4-responsive PKU patients, but possibly also directly improves neurocognitive functioning in both BH4-responsive and BH4-unresponsive PKU patients. In the present review, we aim to further define the theoretical working mechanisms by which BH4 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 BH4 treatment regimen to directly improve neurocognitive functioning in PKU. Such possible repurposing approach of BH4 treatment in PKU may improve neuropsychological outcome and mental health in both BH4-responsive and BH4-unresponsive PKU patients.

Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalJournal of Inherited Metabolic Disease
Volume43
Issue number2
Early online date1-Aug-2019
Publication statusPublished - Mar-2020

    Keywords

  • phenylketonuria, tetrahydrobiopterin, treatment, brain, neurocognitive functioning, neurotransmitters, EARLY-TREATED PHENYLKETONURIA, CEREBRAL GLUCOSE-METABOLISM, NITRIC-OXIDE SYNTHASE, GLUTAMATERGIC SYNAPTIC-TRANSMISSION, DOPAMINE-RELEASING ACTION, OXIDATIVE STRESS, L-PHENYLALANINE, RAT STRIATUM, ENDOTHELIAL DYSFUNCTION, SERUM PHENYLALANINE

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