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Journal of Inherited Metabolic Disease

, Volume 39, Issue 5, pp 733–741 | Cite as

The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies

  • Déborah Mathis
  • Lucia Abela
  • Monique Albersen
  • Céline Bürer
  • Lisa Crowther
  • Karin Beese
  • Hans Hartmann
  • Levinus A. Bok
  • Eduard Struys
  • Sorina M. Papuc
  • Anita Rauch
  • Martin Hersberger
  • Nanda M. Verhoeven-Duif
  • Barbara PleckoEmail author
Original Article

Abstract

Background

Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B6-dependent epilepsy. As these defects interfere with vitamin B6 metabolism by different mechanisms, the plasma vitamin B6 profile can give important clues for further molecular work-up. This has so far been investigated in only a small number of patients.

Methods

We evaluated the vitamin B6 vitamers pyridoxal 5’-phosphate (PLP), pyridoxal (PL), pyridoxamine (PM), pyridoxine (PN) and the catabolite pyridoxic acid (PA) in the so far largest patient cohort: reference (n = 50); pyridox(am)ine 5’-phosphate oxidase (PNPO) deficiency (n = 6); antiquitin (ATQ) deficiency (n = 21); tissue non-specific alkaline phosphatase (TNSALP) deficiency (n = 2) and epileptic encephalopathy (EE) of unknown etiology tested negative for ATQ and PNPO deficiency (n = 64).

Results

High plasma PM concentration was found in all patients with PNPO deficiency irrespective of vitamin B6 supplementation. Their PM concentration and the PM/PA ratio was significantly higher (p < 0.0001), compared to any other patients analysed. One patient with TNSALP deficiency and sampling prior to PN supplementation had markedly elevated plasma PLP concentration. On PN supplementation, patients with TNSALP deficiency, ATQ deficiency and patients of the EE cohort had similar plasma vitamin B6 profiles that merely reflect the intake of supra-physiological doses of vitamin B6. The interval of sampling to the last PN intake strongly affected the plasma concentrations of PN, PL and PA.

Conclusions

PM concentrations and the PM/PA ratio clearly separated PNPO-deficient patients from the other cohorts. The plasma PM/PA ratio thus represents a robust biomarker for the selective screening of PNPO deficiency.

Keywords

Epileptic Encephalopathy Hypophosphatasia Healthy Proband Pyridox Pyridoxic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank B. Schmitt, G. Wohlrab, J. Fluss, K. Fuhrer, J. Häberle, O. Hasselmann, I. Kern, O. Maier, F. Martin, M. Steinlin, G. Visser, F.C. Hofstede and P.M. van Hasselt for kindly providing us with patient samples and T. Roser and M. Bosma for analysing plasma vitamin B6 profiles.

Compliance with ethical standards

Conflict of interest

None.

Supplementary material

10545_2016_9955_MOESM1_ESM.doc (592 kb)
ESM 1 (DOC 591 kb)

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Copyright information

© SSIEM 2016

Authors and Affiliations

  • Déborah Mathis
    • 1
  • Lucia Abela
    • 2
    • 3
    • 4
  • Monique Albersen
    • 5
  • Céline Bürer
    • 6
  • Lisa Crowther
    • 2
    • 3
    • 4
  • Karin Beese
    • 1
  • Hans Hartmann
    • 7
  • Levinus A. Bok
    • 8
  • Eduard Struys
    • 9
  • Sorina M. Papuc
    • 3
    • 4
    • 10
  • Anita Rauch
    • 3
    • 4
    • 10
  • Martin Hersberger
    • 1
  • Nanda M. Verhoeven-Duif
    • 5
  • Barbara Plecko
    • 2
    • 3
    • 4
    Email author
  1. 1.Division of Clinical Chemistry and BiochemistryUniversity Children’s Hospital ZurichZurichSwitzerland
  2. 2.Division of Child NeurologyUniversity Children’s Hospital ZurichZurichSwitzerland
  3. 3.Children’s Research CentreUniversity Children’s Hospital ZurichZurichSwitzerland
  4. 4.Radiz - Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare DiseasesUniversity of ZurichZurichSwitzerland
  5. 5.Department of GeneticsUniversity Medical Center (UMC) UtrechtUtrechtNetherlands
  6. 6.Division of MetabolismUniversity Children’s Hospital ZurichZurichSwitzerland
  7. 7.Department of PediatricsHannover Medical SchoolHannoverGermany
  8. 8.Department of PediatricsMMCVeldhovenNetherlands
  9. 9.Metabolic Unit, Department of Clinical ChemistryVU University Medical CenterAmsterdamNetherlands
  10. 10.Institute of Medical GeneticsUniversity of ZurichZurichSwitzerland

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