title: Normal Cerebrospinal Fluid Pyridoxal 5'-Phosphate Level in a PNPO-Deficient Patient with Neonatal-Onset Epileptic Encephalopathy.
abstract: Deficiency of pyridox(am)ine 5'-phosphate oxidase (PNPO, OMIM 610090) is a treatable autosomal recessive inborn error of metabolism. Neonatal epileptic encephalopathy and a low cerebrospinal fluid (CSF) pyridoxal 5'-phosphate level are the reported hallmarks of PNPO deficiency, but its clinical and biochemical spectra are not fully known.
  
  
  METHODS
  A girl born at 33 3/7 weeks of gestation developed seizures in the first hours of life. Her seizures initially responded to GABAergic agonists, but she subsequently developed a severe epileptic encephalopathy. Brain MRI and infectious and metabolic evaluations at birth, including urinary alpha-aminoadipic semialdehyde (AASA), were normal. Lumbar puncture at age 3 months showed: pyridoxal 5'-phosphate, 52 nmol/L (normal, 23-64); homovanillic acid, 392 nmol/L (normal, 450-1,132); 5-hydroxyindoleacetic acid, 341 nmol/L (normal, 179-711); and 3-ortho-methyldopa, 30 nmol/L (normal, below 300). The patient was not being treated with pyridoxine nor with pyridoxal 5'-phosphate at the time of the lumbar puncture. She died at age 14 months. A sequencing panel targeting 53 epilepsy-related genes revealed a homozygous missense mutation in PNPO (c.674G>A, p.R225H). Homozygosity was confirmed by parental testing. Expression studies of mutant p.R225H PNPO revealed greatly reduced activity. In conclusion, a normal CSF level of pyridoxal 5'-phosphate does not rule out PNPO deficiency.
authors.affiliation: Divisions of Medical Genetics (AL, AML, CBG, GM) and Neurology (PD, ER), Department of Paediatrics, Biochemical Genetics Laboratory (CBG, PA), CHU Sainte-Justine and Université de Montréal, 3175 Côte-Sainte-Catherine, Montreal, QC, Canada, H3T 1C5.
authors.forename: Alina
authors.initials: A
authors.lastname: Levtova
authors.forename: Stephane
authors.initials: S
authors.lastname: Camuzeaux
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Laberge
authors.forename: Pierre
authors.initials: P
authors.lastname: Allard
authors.forename: Catherine
authors.initials: C
authors.lastname: Brunel-Guitton
authors.forename: Paola
authors.initials: P
authors.lastname: Diadori
authors.forename: Elsa
authors.initials: E
authors.lastname: Rossignol
authors.forename: Keith
authors.initials: K
authors.lastname: Hyland
authors.forename: Peter T
authors.initials: PT
authors.lastname: Clayton
authors.forename: Philippa B
authors.initials: PB
authors.lastname: Mills
authors.forename: Grant A
authors.initials: GA
authors.lastname: Mitchell