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Partial Pyridoxine Responsiveness in PNPO Deficiency

  • Phillip L. Pearl
  • Keith Hyland
  • J Chiles
  • Colleen L McGavin
  • Yuezhou Yu
  • Donald Taylor
Case Report
Part of the JIMD Reports book series (JIMD, volume 9)

Abstract

Objective: Autosomal-recessive pyridox(am)ine phosphate oxidase (PNPO) deficiency causes pyridoxal-5-phosphate (PLP)-dependent epilepsy. We describe partial PNPO deficiency with a transient response to pyridoxine (B6).

Methods: CSF neurotransmitter metabolites, PLP, and amino acids were analyzed while the patient was receiving pyridoxine. PNPO gene sequencing was performed by standard techniques.

Results: A full-term 3,220 g male with refractory neonatal seizures became seizure free for 6 weeks on pyridoxine (B6). Breakthrough seizures followed. These stopped upon the first dose of PLP although episodes occurred as a dose became due. An unidentified peak was detected on the chromatographic system used to measure CSF PLP. PNPO gene sequencing identified a homozygous mutation in a highly conserved area in exon 3: c.352G>A p.G118R, predicting substitution of arginine for glycine. At age 28 months the child has hypotonia and developmental delay, both mild in severity.

Conclusions: Transient pyridoxine responsiveness may be seen in partial PNPO deficiency. A CSF metabolite peak, likely pyridoxine phosphate, is identifiable in patients with PNPO deficiency who are taking supplemental pyridoxine. Partial B6 responsiveness is an indication for possible PNPO deficiency and trial of PLP.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Phillip L. Pearl
    • 1
    • 4
  • Keith Hyland
    • 2
  • J Chiles
    • 2
  • Colleen L McGavin
    • 1
  • Yuezhou Yu
    • 1
  • Donald Taylor
    • 3
  1. 1.Department of Neurology, Children’s National Medical CenterGeorge Washington University School of MedicineWashington, DCUSA
  2. 2.Medical NeurogeneticsAtlantaUSA
  3. 3.Child Neurology AssociatesRichmondUSA
  4. 4.Department of NeurologyChildren’s National Medical CenterWashington, DCUSA

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