Normal Cerebrospinal Fluid Pyridoxal 5'-Phosphate Level in a PNPO-Deficient Patient with Neonatal-Onset Epileptic Encephalopathy

JIMD Reports
Alina LevtovaGrant A Mitchell

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. 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 te...Continue Reading

Citations

Aug 13, 2017·Journal of Inherited Metabolic Disease·Rúben J RamosNanda M Verhoeven-Duif
Jun 28, 2016·Journal of Inherited Metabolic Disease·Déborah MathisBarbara Plecko
Jan 24, 2019·Journal of Inherited Metabolic Disease·Matthew P WilsonPeter T Clayton
Jul 2, 2019·Human Molecular Genetics·Wanhao ChiXiaoxi Zhuang
Nov 25, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Jolita CiapaiteNanda M Verhoeven-Duif

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