Typical and atypical phenotypes of PNPO deficiency with elevated CSF and plasma pyridoxamine on treatment

Dev Med Child Neurol. 2014 May;56(5):498-502. doi: 10.1111/dmcn.12346. Epub 2013 Nov 23.

Abstract

Pyridox(am)ine phosphate oxidase (PNPO) deficiency causes severe early infantile epileptic encephalopathy and has been characterized as responding to pyridoxal-5'-phosphate but not to pyridoxine. Two males with PNPO deficiency and novel PNPO mutations are reported and their clinical, metabolic, and video-electroencephalographic (EEG) findings described. The first child showed electro-clinical responses to pyridoxine and deterioration when pyridoxine was withheld. At last review, he has well-controlled epilepsy with pyridoxal-5'-phosphate monotherapy and an autism spectrum disorder. The second child had a perinatal middle cerebral artery infarct and a myoclonic encephalopathy. He failed to respond to pyridoxine but responded well to pyridoxal-5'-phosphate. At the age of 21 months he has global developmental delay and hemiparesis but is seizure-free with pyridoxal-5'-phosphate monotherapy. Plasma and cerebrospinal fluid pyridoxamine levels were increased in both children during treatment with pyridoxine or pyridoxal-5'-phosphate. These observations indicate that differential responses to pyridoxine and pyridoxal-5'-phosphate treatment cannot be relied upon to diagnose PNPO deficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases, Metabolic* / drug therapy
  • Brain Diseases, Metabolic* / metabolism
  • Brain Diseases, Metabolic* / physiopathology
  • Child
  • Child, Preschool
  • Electroencephalography
  • Humans
  • Hypoxia-Ischemia, Brain* / drug therapy
  • Hypoxia-Ischemia, Brain* / metabolism
  • Hypoxia-Ischemia, Brain* / physiopathology
  • Male
  • Pyridoxal Phosphate / therapeutic use*
  • Pyridoxamine / blood*
  • Pyridoxamine / cerebrospinal fluid*
  • Pyridoxaminephosphate Oxidase / deficiency*
  • Pyridoxaminephosphate Oxidase / metabolism
  • Seizures* / drug therapy
  • Seizures* / metabolism
  • Seizures* / physiopathology
  • Vitamin B Complex / therapeutic use*

Substances

  • Vitamin B Complex
  • Pyridoxal Phosphate
  • Pyridoxamine
  • Pyridoxaminephosphate Oxidase

Supplementary concepts

  • Pyridoxamine 5-Prime-Phosphate Oxidase Deficiency