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Vitamin B6-Dependent and Responsive Disorders

  • Barbara PleckoEmail author
  • Eduard A. Struys
  • Cornelis Jakobs

Abstract

The importance of vitamin B6 is evident by its role as the most abundant cofactor in human metabolism. A total of six different B6 vitamers follow a complex pathway of absorption and transformation into the final active cofactor, pyridoxal 5′-phosphate (PLP), which catalyses over 100 reactions, mainly in amino acid and neurotransmitter metabolism. Over recent years a number of genetic defects have been identified as the underlying cause of vitamin B6-dependent epilepsies that need to be considered particularly in neonatal, therapy-resistant seizures of unclear aetiology. With diagnostic delay these disorders can be fatal or may lead to irreversible brain damage. Therefore, a standardised vitamin B6 trial should be part of a protocol for neonatal seizures in every institution caring for the critically ill newborn. The underlying mechanisms of vitamin B6-dependent epilepsies can be assigned to either reduced production/availability of PLP or to inactivation of PLP by accumulating compounds and formation of a Knoevenagel product. The disorders can be distinguished by specific biomarkers in urine, plasma or CSF and confirmed by molecular testing. Affected patients need a lifelong oral treatment with pyridoxine or pyridoxal 5′-phosphate and withdrawal will inevitably lead to recurrence of seizure. Due to autosomal recessive inheritance, recurrence risk for all disorders discussed here is 25 % and intrauterine treatment with vitamin B6 administered to the mother from early pregnancy may be considered in forthcoming pregnancies. Prenatal testing is available by molecular analysis.

Keywords

Status Epilepticus Sulfite Oxidase Irreversible Brain Damage ALDH7A1 Gene Ohtahara Syndrome 
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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Barbara Plecko
    • 1
    Email author
  • Eduard A. Struys
    • 2
  • Cornelis Jakobs
    • 3
  1. 1.Department of Pediatric NeurologyChildren’s Hospital, University of ZürichZürichSwitzerland
  2. 2.Metabolic Unit, Clinical ChemistryVUmc Medical CenterAmsterdamThe Netherlands
  3. 3.Department Clinical Chemistry, PK 1X 014VU University Medical Center AmsterdamAmsterdamThe Netherlands

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