Inborn errors in the vitamin B6 salvage enzymes associated with neonatal epileptic encephalopathy and other pathologies.

  title={Inborn errors in the vitamin B6 salvage enzymes associated with neonatal epileptic encephalopathy and other pathologies.},
  author={Mohini S. Ghatge and Mohammed H. AL Mughram and Abdelsattar M. Omar and Martin K. Safo},
Diet modifies allele-specific phenotypes in Drosophila carrying epilepsy-associated PNPO variants
It is demonstrated that human PNPO variants interact with diet to contribute to phenotypic variations; and that the knock-in Drosophila model offers a powerful approach to systematically examine clinical manifestations and the underlying mechanisms of human PnPO deficiency.
Drosophila carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes
It is shown that phenotypes in knock-in flies are allele and diet dependent, providing clues for timely and specific diet interventions and biological insights into mechanisms underlying phenotypic variations and specific therapeutic strategies.


Disorders affecting vitamin B6 metabolism
The clinical and biochemical features of disorders leading to B6‐responsive seizures and the treatment of these disorders are described in this review.
Molecular characterization of pyridoxine 5′-phosphate oxidase and its pathogenic forms associated with neonatal epileptic encephalopathy
It is revealed that human PNPO has an allosteric PLP binding site that plays a crucial role in the enzyme regulation and therefore in the regulation of vitamin B6 metabolism in humans.
Biomedical aspects of pyridoxal 5'-phosphate availability.
The biologically active form of vitamin B6, pyridoxal 5'-phosphate, is a cofactor in over 160 enzyme activities involved in a number of metabolic pathways, including neurotransmitter synthesis and degradation, and represents a very challenging research field.
Pyridoxamine Supplementation Effectively Reverses the Abnormal Phenotypes of Zebrafish Larvae With PNPO Deficiency
Zebrafish is suggested to be a promising PNPO-deficiency model for studying PLP homeostasis and drug therapy in vivo, and pyridoxamine (PM), another dietary form of vitamin B6, showed rescue effects even at a lower concentration than PLP, presenting a possible new therapeutic treatment for PN PO-deficient NEE.
Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase.
Maintenance of optimal PLP levels in the brain may be important in many neurological disorders in which neurotransmitter metabolism is disturbed (either as a primary or as a secondary phenomenon).
Pyridoxine supply in human development.
  • F. Bowling
  • Biology, Medicine
    Seminars in cell & developmental biology
  • 2011
Molecular Basis of Reduced Pyridoxine 5′-Phosphate Oxidase Catalytic Activity in Neonatal Epileptic Encephalopathy Disorder*
The results provide a molecular basis for the phenotype associated with the R229W mutation, as well as providing a foundation for understanding the pathophysiological consequences of pyridoxine 5′-phosphate oxidase mutations.
Inborn errors affecting vitamin B6 metabolism
The clinical features and biochemistry of three inborn errors of metabolism affecting brain pyridoxal 5-phosphate concentrations are described, each of which cause early-onset epilepsy of variable severity.