Journal Article

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

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

2016

Overview

Background Recent decades have unravelled the molecular background of a number of inborn errors of metabolism (IEM) causing vitamin B 6 -dependent epilepsy. As these defects interfere with vitamin B 6 metabolism by different mechanisms, the plasma vitamin B 6 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 B 6 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 B 6 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 B 6 profiles that merely reflect the intake of supra-physiological doses of vitamin B 6 . 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.

• Publisher: Springer Netherlands
• Subject: Adolescent / Adult / Biochemistry / Biomarkers - blood / Child / Child, Preschool / Female / Human Genetics / Humans / Infant / Infant, Newborn / Internal Medicine / Male / Medicine / Medicine & Public Health / Metabolic Diseases / Metabolism, Inborn Errors - blood / Original Article / Pediatrics / Plasma - chemistry / Pyridoxal - blood / Pyridoxal Phosphate - analogs & derivatives / Pyridoxal Phosphate - blood / Pyridoxamine - blood / Pyridoxic Acid - blood / Pyridoxine - blood / Spasms, Infantile - blood / Vitamin B 6 - blood / Young Adult