BH4 treatment in BH4-responsive PKU patients
| Autor: | Rianne Jahja, Karen Anjema, Francjan J. van Spronsen, Ido P. Kema, M. Rebecca Heiner-Fokkema, Geertje B. Liemburg, Terry G J Derks, Danique van Vliet, Martijn de Groot, Eddy A. van der Zee |
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| Přispěvatelé: | Van der Zee lab, Center for Liver, Digestive and Metabolic Diseases (CLDM), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Lifestyle Medicine (LM) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Phenylalanine hydroxylase Endocrinology Diabetes and Metabolism Dopamine PHENYLKETONURIC PATIENTS Phenylalanine Biochemistry METABOLITES chemistry.chemical_compound Endocrinology Phenylketonurias Internal medicine Genetics medicine Humans Phenylketonuria TYROSINE-HYDROXYLASE BRAIN Child Neurotransmitter Molecular Biology SERUM PROLACTIN Retrospective Studies Tetrahydrobiopterin biology Tyrosine hydroxylase business.industry PHENYLALANINE SEROTONIN Inborn error of metabolism Neurotransmitters Biopterin Prolactin DEFICIENCY CATECHOLAMINES chemistry biology.protein Female Serotonin business medicine.drug |
| Zdroj: | Molecular Genetics and Metabolism, 114(1), 29-33. ACADEMIC PRESS INC ELSEVIER SCIENCE |
| ISSN: | 1096-7192 |
| Popis: | In phenylketonuria (PKU), cerebral neurotransmitter deficiencies have been suggested to contribute to brain dysfunction. Present treatment aims to reduce blood phenylalanine concentrations by a phenylalanine-restricted diet, while in some patients blood phenylalanine concentrations also respond to cofactor treatment with tetrahydrobiopterin (BH4). Recently, a repurposing approach of BH4 was suggested to increase cerebral neurotransmitter synthesis. To investigate whether BH4 may improve cerebral dopamine concentrations in PKU patients beyond its effect through lowering blood phenylalanine concentrations, we investigated blood prolactin concentrations-as a parameter of brain dopamine availability. We retrospectively compared blood prolactin in relation to blood phenylalanine concentrations of nine (male) BH4-responsive PKU patients, when being treated without and with BH4. Blood prolactin concentrations positively correlated to blood phenylalanine concentrations (p=0.002), being significantly lower with than without BH4 treatment (p=0.047). In addition, even in this small number of male patients, blood prolactin concentrations tended to be lower at increasing BH4 dose (p=0.054), while taking blood phenylalanine concentrations into account (p=0.002). In individual BH4-responsive patients, median blood prolactin concentrations were significantly lower while using BH4 than before using BH4 treatment (p=0.024), whereas median blood phenylalanine concentrations tended to be lower, but this did not reach statistical significance (p=0.107). Therefore, these data show that high blood phenylalanine in BH4-responsive PKU male patients seems to be associated with increased blood prolactin concentrations, suggesting reduced cerebral dopamine availability. Moreover, these data suggest that BH4 treatment in itself could decrease blood prolactin concentrations in a dose-responsive way, independent of blood phenylalanine concentrations. We conclude that these preliminary data indicate that BH4 treatment may improve cerebral dopamine concentrations in PKU patients beyond its effect through lowering blood phenylalanine concentrations, possibly in a dose-dependent manner, but further research would be warranted. |
| Databáze: | OpenAIRE |
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