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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Late-onset drug-resistant epilepsy in pyridoxamine 5'-phosphate oxidase deficiency: a case report.
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Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Background: Pyridoxamine 5'-phosphate oxidase deficiency is a rare inborn error of vitamin B metabolism that presents with drug-resistant epileptic seizures. However, the condition is responsive to supplementation with the active vitamin B metabolite pyridoxal 5'-phosphate and, in some cases, pyridoxine.
Case Presentation: In this case report, a 10-year-old Iranian male of Fars ethnicity came to a regional hospital in Tehran, Iran with a chief complaint of tic-like movement.
On pathways and blind alleys-The importance of biomarkers in vitamin B -dependent epilepsies.
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Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
Over the past two decades, the field of vitamin B -dependent epilepsies has evolved by the recognition of a growing number of gene defects (ALDH7A1, PNPO, ALPL, ALDH4A1, PLPBP as well as defects of the glycosylphosphatidylinositol anchor proteins) that all lead to reduced availability of pyridoxal 5'-phosphate, an important cofactor in neurotransmitter and amino acid metabolism. In addition, positive pyridoxine response has been observed in other monogenic defects such as MOCS2 deficiency or KCNQ2 and there may be more defects to be discovered. Most entities lead to neonatal onset pharmaco-resistant myoclonic seizures or even status epilepticus and pose an emergency to the treating physician.
View Article and Find Full Text PDFEpilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review.
Children (Basel)
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Child Neurology and Psychiatry Unit, Department of Human Neurosciences, Sapienza University of Rome, 00185 Rome, Italy.
Background: Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects).
Patients And Methods: We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected.
Ohtahara and West Syndrome due to Pyridox(am)ine-5-Phosphate Oxidase (PNPO) Deficiency with Novel Phenotype and Good Outcome without Pyridoxal-5'-Phosphate.
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Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Near NIMHANS, Bengaluru, Karnataka, 560029, India.
The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study.
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Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Neurology and Clinical Neurophysiology, St. Olav University Hospital, Trondheim, Norway. Electronic address:
Background: Pyridoxine-dependent epilepsy (PDE) is a rare seizure disorder usually presenting with neonatal seizures. Most cases are caused by biallelic pathogenic ALDH7A1variants. While anti-seizure medications are ineffective, pyridoxine provides seizure control, and dietary interventions may be of benefit.
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