Abstract
BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations. MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV). ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher. ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.
Highlights
Phenylketonuria (PKU; OMIM #261600) is an autosomal recessive inborn error caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH), which normally converts phenylalanine (Phe) into tyrosine (Tyr)
This study investigated the effects of BH4 on diurnal and day-to-day variations of blood Phe and Tyr concentrations in proven BH4 responsive PKU patients
During regimen 1, patients returned to their former protein restricted diet with Phe-free protein substitute
Summary
Phenylketonuria (PKU; OMIM #261600) is an autosomal recessive inborn error caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH), which normally converts phenylalanine (Phe) into tyrosine (Tyr). Using BH4, these BH4 responsive PKU patients are able to decrease their blood Phe concentrations and/or liberalize dietary treatment [15,16]. There are some data indicating that BH4 does decrease blood Phe concentrations (in BH4 responsive PKU patients) and results in less variability in blood Phe concentrations [17,18,19]. This study investigated the effects of BH4 on diurnal and day-to-day variations of blood Phe and Tyr concentrations in proven BH4 responsive PKU patients. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations. Conclusion: BH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
