2. Academic Validation
  3. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism

PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism

  • Mol Genet Metab. 2008 Aug;94(4):431-434. doi: 10.1016/j.ymgme.2008.04.008.
Morad Khayat 1,  Stanley H Korman 2,  Pnina Frankel 1,  Zalman Weintraub 3,  Sylvia Hershckowitz 4,  Vered Fleisher Sheffer 4,  Mordechai Ben Elisha 4,  Ronald A Wevers 5,  Tzipora C Falik-Zaccai 6
Affiliations

Affiliations

  • 1 Institute of Medical Genetics, Western Galilee Hospital, Nahariya, P.O. Box 21, 22100 Nahariya, Israel.
  • 2 Metabolic Diseases Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 3 Department of Neonatology, Western Galilee Hospital, Nahariya, Israel; Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
  • 4 Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
  • 5 Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, The Netherlands.
  • 6 Institute of Medical Genetics, Western Galilee Hospital, Nahariya, P.O. Box 21, 22100 Nahariya, Israel; Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
PMID: 18485777 DOI: 10.1016/j.ymgme.2008.04.008
Abstract

The rare autosomal recessive disorder pyridoxine 5'-phosphate oxidase (PNPO) deficiency is a recently described cause of neonatal and infantile seizures. Clinical evaluation, and biochemical and genetic testing, were performed on a neonate with intractable seizures who did not respond to anticonvulsant drugs and pyridoxine. Sequencing of the PNPO gene revealed a novel homozygous c.284G>A transition in exon 3, resulting in arginine to histidine substitution and reduced activity of the PNPO mutant to 18% relative to the wild type. This finding enabled molecular prenatal diagnosis in a subsequent pregnancy, accurate genetic counseling in the large inbred family, and population screening.

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