Pyridox(am)ine-5-Phosphate Oxidase Deficiency Treatable Cause of Neonatal Epileptic Encephalopathy With Burst Suppression

Abstract

Pyridox(am)ine-5-phosphate oxidase deficiency is an autosomal recessive disorder of pyridoxine metabolism. Intractable neonatal epileptic encephalopathy is the classical presentation. Pyridoxal-5-phosphate or pyridoxine supplementation improves symptoms. We report a patient with myoclonic and tonic seizures at the age of 1 hour. Pyridoxal-5-phosphate was started on the first day of life and seizures stopped at the age of 3 days, but encephalopathy persisted for 4 weeks. She had normal neurodevelopmental outcome at the age of 12 months on pyridoxal-5-phosphate monotherapy. She had novel homozygous pathogenic frameshift mutation (c.448_451del;p.Pro150Argfs*27) in the PNPO gene. Long-lasting encephalopathy despite well-controlled clinical seizures does neither confirm nor exclude pyridox(am)ine-5-phosphate oxidase deficiency. Normal neurodevelopmental outcome of our patient emphasizes the importance of pyridoxal-5-phosphate treatment. Pyridox(am)ine-5-phosphate oxidase deficiency should be included in the differential diagnosis of Ohtahara syndrome and neonatal myoclonic encephalopathy as a treatable underlying cause. In addition, we reviewed the literature for pyridox(am)ine-5-phosphate oxidase deficiency and summarized herein all confirmed cases.

Diagnostic yield of genetic testing in epileptic encephalopathy in childhood

“…The IMDs in these patients included pyridoxine dependent epilepsy (PDE) caused by ALDH7A1 genetic defect (PDE‐ ALDH7A1 ), Menkes disease, pyridox(am)ine‐5‐phosphate oxidase (PNPO) deficiency, cobalamin G deficiency, severe methylenetetrahydrofolate reductase (MTHFR) deficiency, glucose transporter 1 (GLUT1) deficiency, glycine encephalopathy, and pyruvate dehydrogenase complex (PDHC) deficiency. All patients had either clinical (e.g., Menkes disease with brittle hair) or biochemical features (e.g., GLUT1 deficiency with low CSF glucose level) suggestive of the underlying IMD.…”

“…In this group, 50% of the patients had one of the treatable IMD including PNPO deficiency, PDE‐ ALDH7A1 , cobalamin G deficiency and severe MTHFR deficiency. The treated PNPO deficient patient has normal neurodevelopment at the age of 1 year and has been seizure‐free on pyridoxal‐5‐phosphate monotherapy since the neonatal period . The PDE‐ ALDH7A1 patient has mild gait ataxia with normal cognitive functions at the age of 2 and a half years and has been seizure‐free on pyridoxine monotherapy and lysine‐restricted diet .…”

Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

“…Whilst the long-term outcome is variable, most children have a degree of developmental delay involving cognitive impairment and speech and language problems. However, a recent review reports 31% of patients having normal developmental outcome (Guerin et al 2014).…”

Neurodevelopmental Outcomes Based on Electroencephalographic Morphology with Suppression Bursts

“…In patients with metabolic disorders and SBs, pyridox(am)ine-5-phosphate oxidase deficiency and pyridoxine-dependent epilepsy should be included in the differential diagnosis of neonatal SB EEG as treatable underlying causes [19]. In addition, some patients with SBs had a biotinidase deficiency, and their epilepsy was controlled using biotin and adjunctive antiepilepsy agents.…”