title: PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism.
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.
authors.affiliation: Institute of Medical Genetics, Western Galilee Hospital, Nahariya, P.O. Box 21, 22100 Nahariya, Israel.
authors.forename: Morad
authors.initials: M
authors.lastname: Khayat
authors.affiliation: Metabolic Diseases Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Korman
authors.affiliation: Institute of Medical Genetics, Western Galilee Hospital, Nahariya, P.O. Box 21, 22100 Nahariya, Israel.
authors.forename: Pnina
authors.initials: P
authors.lastname: Frankel
authors.affiliation: Department of Neonatology, Western Galilee Hospital, Nahariya, Israel; Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Zalman
authors.initials: Z
authors.lastname: Weintraub
authors.affiliation: Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hershckowitz
authors.affiliation: Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
authors.forename: Vered Fleisher
authors.initials: VF
authors.lastname: Sheffer
authors.affiliation: Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
authors.forename: Mordechai Ben
authors.initials: MB
authors.lastname: Elisha
authors.affiliation: Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Wevers
authors.affiliation: 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.
authors.forename: Tzipora C
authors.initials: TC
authors.lastname: Falik-Zaccai
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D018389:Codon, Nonsense; D003241:Consanguinity; D006224:Cricetinae; D003412:Cricetulus; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D015870:Gene Expression; D005820:Genetic Testing; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D016297:Mutagenesis, Site-Directed; D010375:Pedigree; D017354:Point Mutation; D011296:Prenatal Diagnosis; D011734:Pyridoxaminephosphate Oxidase / Q000172:deficiency* / Q000235:genetics; D011736:Pyridoxine / Q000378:metabolism*; D012640:Seizures / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D011734:Pyridoxaminephosphate Oxidase; D011736:Pyridoxine