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Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine

  • Metabolic Diseases
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Abstract

Seven phenylketonuria (PKU) patients aged 15–24 years were allowed unrestricted diet for 3 weeks. Three of these patients performed well on unrestricted diet according to visual reaction time variability (RTv 50–100 ms) and did not show significant changes when returning to the phenylalanine-restricted diet (RTv 70–100 ms). Neither did the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) change significantly. Four of the patients, however, performed rather poorly (RTv 120–220 ms) on unrestricted diet and improved significantly (P<0.03) when the diet was restored (RTv 70–150 ms). The improvements were accompanied by significant (P<0.01 and P<0.02) increases (mean 52% and 109%) in CSF levels of HVA and 5-HIAA. Five PKU patients aged 15–23 years were allowed unrestricted diet or unrestricted diet supplemented with various amounts of tyrosine (106–194 mg/kg per 24 h). Two of these patients performed very well on unrestricted diet (RTv 60 ms) and showed little change when the unrestricted diet was supplemented with tyrosine (RTv 70 ms and 80 ms). The three other patients, who performed rather poorly (RTv 120–220 ms), improved significantly (P<0.03) when the unrestricted diet was supplemented with tyrosine (RTv 70–140 ms). HVA in CSF increased significantly (P<0.01) with the tyrosine supplement when the amount exceeded a threshold of approximately 80 mg/kg per 24 h. The simultaneous increase in CSF level of 5-HIAA showed a positive correlation (r=0.90; P<0.02) with the increase in HVA concentration suggesting a functional interrelation between the dopaminergic and the serotoninergic nervous systems.

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Abbreviations

PKU:

phenylketonuria

RTy:

reaction time variability

HVA:

homovanillic acid

5-HIAA:

5-hydroxyindoleacetic acid

CSF:

cerebrospinal fluid

IQ:

intelligence quotient

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Authors and Affiliations

  1. Søkæret 8, Annisse, DK-3200, Helsinge, Denmark

    C. Lykkelund

  2. The John F. Kennedy Institute, Gl. Landevej 7, DK-2600, Glostrup, Denmark

    J. B. Nielsen, H. C. Lou, V. Rasmussen, A. M. Gerdes & F. Güttler

  3. Section of Clinical Genetics, Rigshospitalet, DK-2100, Copenhagen Ø, Denmark

    E. Christensen

Authors
  1. C. Lykkelund
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  2. J. B. Nielsen
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  3. H. C. Lou
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  4. V. Rasmussen
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  5. A. M. Gerdes
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  6. E. Christensen
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  7. F. Güttler
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Lykkelund, C., Nielsen, J.B., Lou, H.C. et al. Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine. Eur J Pediatr 148, 238–245 (1988). https://doi.org/10.1007/BF00441411

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  • DOI: https://doi.org/10.1007/BF00441411

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