nach oben

Erschienen in:

24.06.2016 | Original Article

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

verfasst von: 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

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

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.

Nur mit Berechtigung zugänglich

Albersen M, Bosma M, Knoers NV et al (2013) The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. PLoS One 8, e54113CrossRefPubMedPubMedCentral

Albersen M, Bosma M, Jans JJ et al (2015) Vitamin B6 in plasma and cerebrospinal fluid of children. PLoS One 10, e0120972CrossRefPubMedPubMedCentral

Apeland T, Mansoor MA, Pentieva K, McNulty H, Strandjord RE (2003) Fasting and post-methionine loading concentrations of homocysteine, vitamin B2, and vitamin B6 in patients on antiepileptic drugs. Clin Chem 49:1005–1008CrossRefPubMed

Bagci S, Zschocke J, Hoffmann GF, et al (2009) Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. BMJ Case Rep 2009

Bor MV, Refsum H, Bisp MR et al (2003) Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: a randomized placebo-controlled study. Clin Chem 49:155–161CrossRefPubMed

Brautigam C, Hyland K, Wevers R et al (2002) Clinical and laboratory findings in twins with neonatal epileptic encephalopathy mimicking aromatic L-amino acid decarboxylase deficiency. Neuropediatrics 33:113–117CrossRefPubMed

Campistol J, Plecko B (2015) Treatable newborn and infant seizures due to inborn errors of metabolism. Epileptic Disord 17(3):229–242PubMed

Clayton PT, Surtees RA, DeVile C, Hyland K, Heales SJ (2003) Neonatal epileptic encephalopathy. Lancet 361:1614CrossRefPubMed

di Salvo ML, Safo MK, Contestabile R (2012) Biomedical aspects of pyridoxal 5’-phosphate availability. Front Biosci (Elite Ed) 4:897–913

Footitt EJ, Heales SJ, Mills PB, Allen GF, Oppenheim M, Clayton PT (2011) Pyridoxal 5’-phosphate in cerebrospinal fluid; factors affecting concentration. J Inherit Metab Dis 34:529–538CrossRefPubMed

Footitt EJ, Clayton PT, Mills K et al (2013) Measurement of plasma B6 vitamer profiles in children with inborn errors of vitamin B6 metabolism using an LC-MS/MS method. J Inherit Metab Dis 36:139–145CrossRefPubMed

Goyal M, Fequiere PR, McGrath TM, Hyland K (2013) Seizures with decreased levels of pyridoxal phosphate in cerebrospinal fluid. Pediatr Neurol 48:227–231CrossRef

Khayat M, Korman SH, Frankel P et al (2008) PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. Mol Genet Metab 94:431–434CrossRefPubMed

Levtova A, Camuzeaux S, Laberge AM et al (2015) Normal cerebrospinal fluid pyridoxal 5’-phosphate level in a PNPO-deficient patient with neonatal-onset epileptic encephalopathy. JIMD Rep 22:67–75CrossRefPubMedPubMedCentral

Litmanovitz RO, Dolfin T et al (2002) Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions. J Inherit Metab Dis 25:35–40CrossRefPubMed

Midttun O, Hustad S, Schneede J, Vollset SE, Ueland PM (2007) Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study. Am J Clin Nutr 86:131–138PubMed

Mills PB, Surtees RA, Champion MP et al (2005) Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5’-phosphate oxidase. Hum Mol Genet 14:1077–1086CrossRefPubMed

Mills PB, Camuzeaux SS, Footitt EJ et al (2014) Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome. Brain 137:1350–1360CrossRefPubMedPubMedCentral

Ormazabal A, Oppenheim M, Serrano M et al (2008) Pyridoxal 5’-phosphate values in cerebrospinal fluid: reference values and diagnosis of PNPO deficiency in paediatric patients. Mol Genet Metab 94:173–177CrossRefPubMed

Plecko B, Paul K, Mills P et al (2014) Pyridoxine responsiveness in novel mutations of the PNPO gene. Neurology 82:1425–1433CrossRefPubMedPubMedCentral

Porri S, Fluss J, Plecko B, Paschke E, Korff CM, Kern I (2014) Positive outcome following early diagnosis and treatment of pyridoxal-5’-phosphate oxidase deficiency: a case report. Neuropediatrics 45:64–68CrossRefPubMed

Quasim T, McMillan DC, Talwar D, Vasilaki A, St JORD, Kinsella J (2005) The relationship between plasma and red cell B-vitamin concentrations in critically-ill patients. Clin Nutr 24:956–960CrossRefPubMed

Ruiz A, Garcia-Villoria J, Ormazabal A et al (2008) A new fatal case of pyridox(am)ine 5’-phosphate oxidase (PNPO) deficiency. Mol Genet Metab 93:216–218CrossRefPubMed

Sakurai T, Asakura T, Matsuda M (1987) Transport and metabolism of pyridoxine and pyridoxal in mice. J Nutr Sci Vitaminol (Tokyo) 33:11–19CrossRef

Thakker KM, Sitren HS, Gregory JF 3rd, Schmidt GL, Baumgartner TG (1987) Dosage form and formulation effects on the bioavailability of vitamin E, riboflavin, and vitamin B-6 from multivitamin preparations. Am J Clin Nutr 45:1472–1479PubMed

van der Ham M, Albersen M, de Koning TJ et al (2012) Quantification of vitamin B6 vitamers in human cerebrospinal fluid by ultra performance liquid chromatography-tandem mass spectrometry. Anal Chim Acta 712:108–114CrossRefPubMed

Verrotti A, Pascarella R, Trotta D, Giuva T, Morgese G, Chiarelli F (2000) Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Epilepsy Res 41:253–257CrossRefPubMed

Vilaseca MA, Monros E, Artuch R et al (2000) Anti-epileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C-- > T mutation of the methylenetetrahydrofolate reductase gene. Eur J Paediatr Neurol 4:269–277CrossRefPubMed

Ware TL, Earl J, Salomons GS et al (2014) Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment. Dev Med Child Neurol 56:498–502CrossRefPubMed

Whyte MP, Mahuren JD, Vrabel LA, Coburn SP (1985) Markedly increased circulating pyridoxal-5’-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. J Clin Invest 76:752–756CrossRefPubMedPubMedCentral

Titel: The value of plasma vitamin B6 profiles in early onset epileptic encephalopathies
verfasst von: 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
Publikationsdatum: 24.06.2016
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 5/2016
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-016-9955-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2016

On the origin of 3-methylglutaconic acid in disorders of mitochondrial energy metabolism

Expanding the molecular diversity and phenotypic spectrum of glycerol 3-phosphate dehydrogenase 1 deficiency

A novel method for determining peroxisomal fatty acid β-oxidation

Tyrosinemia type I and not treatment with NTBC causes slower learning and altered behavior in mice

Genetic cause and prevalence of hydroxyprolinemia

Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome