Epilepsy as a pyridoxine-dependent condition: quantified urinary biomarkers for status evaluation and monitoring antiepileptic treatment.

Abstract

The study testifies an assumption on epilepsy as an inborn error of pyridoxine metabolism and suggests non-invasive quantitative biomarkers for clarified evaluation of clinical status and monitoring an individual treatment by antiepileptic drugs. Urinary parameters of pyridoxal-phosphate (PLP)-dependent tryptophan degradation and the level of 4-pyridoxic acid, the end product of pyridoxine metabolism, were measured by HPLC method with simultaneous ultraviolet and fluorimetric detection in children with different forms of epilepsy and matched healthy controls. The concentrations of compounds formed or metabolized in the course of tryptophan degradation (kynurenines, indoxyl-sulfate) along with correlations between them turned out to be quantitative biomarkers useful for both clarifying patient's clinical state and monitoring antiepileptic treatment. In particular, the value of the ratio of 4-pyridoxic acid to kynurenine appears to be an index of an experienced seizure attack, while the ratio of 3-hydroxyanthranilic acid to 3-hydroxykynurenine reflects activity of kynureninase, the enzyme of critical sensitivity to PLP supply. Growing progressively worse, epilepsy is accompanied by aggravation of PLP-dependent disturbances of tryptophan metabolism and expanding inhibition of kynureninase. The affected pyridoxine metabolism is discussed as an inborn genetic trait in epilepsy in general, rather than a specific sign of pyridoxine-dependent epilepsy solely.

• Authors: Svetlana Dolina, Dov Margalit, Sergey Malitsky, Eugeny Pressman, Aharon Rabinkov
• Journal: Medical hypotheses (Med Hypotheses) Vol. 79 Issue 2 Pg. 157-64 (Aug 2012) ISSN: 1532-2777 [Electronic] United States
• PMID: 22647618 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Anticonvulsants
• Biomarkers
• Pyridoxic Acid
• Pyridoxal Phosphate
• Tryptophan
• Pyridoxine

Topics

• Adolescent
• Anticonvulsants (therapeutic use)
• Biomarkers (urine)
• Child
• Child, Preschool
• Epilepsy (diagnosis, drug therapy, urine)
• Female
• Humans
• Male
• Pyridoxal Phosphate (urine)
• Pyridoxic Acid (urine)
• Pyridoxine (urine)
• Reproducibility of Results
• Sensitivity and Specificity
• Treatment Outcome
• Tryptophan (urine)