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 Plecko

doi:10.1007/s10545-016-9955-8

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 Plecko

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	733–741
Journal	Journal of Inherited Metabolic Disease
Volume	39
Issue number	5
DOIs	https://doi.org/10.1007/s10545-016-9955-8
Publication status	Published - 24 Jun 2016

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Mathis, D., Abela, L., Albersen, M., Bürer, C., Crowther, L., Beese, K., Hartmann, H., Bok, L. A., Struys, E., Papuc, S. M., Rauch, A., Hersberger, M., Verhoeven-Duif, N. M., & Plecko, B. (2016). The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies. Journal of Inherited Metabolic Disease, 39(5), 733–741. https://doi.org/10.1007/s10545-016-9955-8

@article{a8fbbda7d93e4914ac8bf8ed9fb3f379,

title = "The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies",

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.",

author = "D{\'e}borah Mathis and Lucia Abela and Monique Albersen and C{\'e}line B{\"u}rer and Lisa Crowther and Karin Beese and Hans Hartmann and Bok, {Levinus A} and Eduard Struys and Papuc, {Sorina M} and Anita Rauch and Martin Hersberger and Verhoeven-Duif, {Nanda M} and Barbara Plecko",

year = "2016",

month = jun,

day = "24",

doi = "10.1007/s10545-016-9955-8",

language = "English",

volume = "39",

pages = "733–741",

journal = "Journal of Inherited Metabolic Disease",

issn = "0141-8955",

publisher = "Springer Netherlands",

number = "5",

}

Mathis, D, Abela, L, Albersen, M, Bürer, C, Crowther, L, Beese, K, Hartmann, H, Bok, LA, Struys, E, Papuc, SM, Rauch, A, Hersberger, M, Verhoeven-Duif, NM & Plecko, B 2016, 'The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies', Journal of Inherited Metabolic Disease, vol. 39, no. 5, pp. 733–741. https://doi.org/10.1007/s10545-016-9955-8

TY - JOUR

T1 - The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies

AU - Mathis, Déborah

AU - Abela, Lucia

AU - Albersen, Monique

AU - Bürer, Céline

AU - Crowther, Lisa

AU - Beese, Karin

AU - Hartmann, Hans

AU - Bok, Levinus A

AU - Struys, Eduard

AU - Papuc, Sorina M

AU - Rauch, Anita

AU - Hersberger, Martin

AU - Verhoeven-Duif, Nanda M

AU - Plecko, Barbara

PY - 2016/6/24

Y1 - 2016/6/24

N2 - 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.

AB - 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.

U2 - 10.1007/s10545-016-9955-8

DO - 10.1007/s10545-016-9955-8

M3 - Article

C2 - 27342130

SN - 0141-8955

VL - 39

SP - 733

EP - 741

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

IS - 5

ER -

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

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