Epilepsy as a Pyridoxine-Dependent Condition: Quantitative Urinary Biomarkers of Epilepsy. Family Disorders of Pyridoxine Metabolism

Abstract

The affected pyridoxine metabolism is discussed as an inborn genetic sign of epilepsy. In children with different forms of epilepsy and matched healthy controls, the urinary parameters of pyridoxal phosphate-dependent tryptophan degradation were measured by high-performance liquid chromatography (HPLC) method with simultaneous ultraviolet and fluorimetric detection. Concentrations of compounds, which are formed in the course of tryptophan degradation, and correlations between them turned out to be quantitative biomarkers useful for evaluation of patient's condition and monitoring individualized antiepileptic treatment. Accumulation of tryptophan, kynurenine, and neurotoxic 3-hydroxykynurenine, along with reduced kynureninase activity, is characteristic of epileptic patients. Growing progressively worse, epilepsy is accompanied by aggravation of pyridoxal phosphate-dependent disturbances of tryptophan metabolism and further inhibition of kynureninase. In asymptomatic first-degree relatives of epileptic probands, disorders of pyridoxine metabolism are of the same (or even higher) extent as in probands. Long-term pyridoxine treatment (7-10 mg/kg daily) is suggested as safe and effective protective replacement therapy. The protocols of this study have been approved by the ethics committee of Kaplan Hospital (Israel).