Clinical and genetic profile of a cohort of pyridoxamine 5-Phosphate oxidase deficiency – A single-center experience

Abstract

Background: Pyridoxamine 5-phosphate oxidase deficiency (PNPOD) is a rare treatable neonatal epileptic encephalopathy. It is important to raise awareness about this condition to enable early treatment. Methodology: This is a retrospective chart review of PNPOD cases followed at Mafraq Hospital during 2011-September 2017. The inclusion criteria include confirmed homozygous or compound heterozygous mutation in pyridox(am)ine-5-phosphate oxidase (PNPO) gene. Results: Seven cases were identified, all Emiratis from two tribes. Six cases from Tribe A had homozygous genetic variant C.674G>T: P. Arg255 Leu (one is presumed to have the same mutation based on confirmed proband sibling and carrier state of the parents of this sibship). One patient from Tribe B was tested abroad and has a confirmed homozygous pathogenic variant in PNPO gene (details not available). All six patients with the identical mutation are from one Emirati tribe suggest a founder effect. Two neonates treated in the first few days of life had the best clinical outcome of seizure control and neurodevelopment. One mortality (the deceased sibling of a normally developing child with this disease) highlights the great importance of early treatment. The remaining four patients had incomplete seizure control with neurobehavioral delay. Patients with intractable epilepsy and poor neurodevelopment never received pyridoxal 5-phosphate in the 1 st days of life, although they received pyridoxine and other anti-seizure medications. Conclusion: PNPOD is a treatable neonatal epileptic encephalopathy; however, early treatment is essential for optimal outcomes. A management algorithm for intractable neonatal seizures emphasizing the crucial "treat before you diagnose" approach is critical for such cases.