PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism.
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.
Khayat
Morad
M
Institute of Medical Genetics, Western Galilee Hospital, Nahariya, P.O. Box 21, 22100 Nahariya, Israel.
Korman
Stanley H
SH
Metabolic Diseases Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Frankel
Pnina
P
Institute of Medical Genetics, Western Galilee Hospital, Nahariya, P.O. Box 21, 22100 Nahariya, Israel.
Weintraub
Zalman
Z
Department of Neonatology, Western Galilee Hospital, Nahariya, Israel; Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
Hershckowitz
Sylvia
S
Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
Sheffer
Vered Fleisher
VF
Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
Elisha
Mordechai Ben
MB
Department of Neonatology, Western Galilee Hospital, Nahariya, Israel.
Wevers
Ronald A
RA
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, The Netherlands.
Falik-Zaccai
Tzipora C
TC
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.
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
D018389:Codon, Nonsense; D011734:Pyridoxaminephosphate Oxidase; D011736:Pyridoxine