Positive Outcome following Early Diagnosis and Treatment of Pyridoxal-5′-Phosphate Oxidase Deficiency: A Case Report

Abstract

Pyridoxal-5′-phosphate oxidase (PNPO) deficiency is a rare autosomal recessive, vitamin-responsive metabolic disorder causing refractory neonatal seizures that respond to the administration of pyridoxal-5′-phosphate (PLP). There are currently few case studies that have documented the functional outcome in PNPO deficiency, which remains poor in the majority of cases. We present the case of a male infant born at 35 weeks gestation who promptly responded to oral administration of PLP, following resistance to common anticonvulsive therapy and to a pyridoxine trial. Neurological outcome at 21 months is favorable and illustrates the importance of standardized vitamin trials in the acute setting of “therapy-resistant” neonatal seizures. Early recognition of PNPO deficiency and appropriate intervention might be associated with a more favorable outcome than initially considered.

Keywords

newborn - neonatal - vitamin B6 - pyridoxal-phosphate - pyridoxine - seizures - epilepsy

• References

• 1 Gospe Jr SM. Neonatal vitamin-responsive epileptic encephalopathies. Chang Gung Med J 2010; 33 (1) 1-12
• 2 Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis 2006; 29 (2-3) 317-326
• 3 Kuo MF, Wang HS. Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine. Pediatr Neurol 2002; 26 (2) 146-147
• 4 Mills PB, Surtees RA, Champion MP , et al. Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5′-phosphate oxidase. Hum Mol Genet 2005; 14 (8) 1077-1086
• 5 Ruiz A, García-Villoria J, Ormazabal A , et al. A new fatal case of pyridox(am)ine 5′-phosphate oxidase (PNPO) deficiency. Mol Genet Metab 2008; 93 (2) 216-218
• 6 Bagci S, Zschocke J, Hoffmann GF , et al. Pyridoxal phosphate-dependent neonatal epileptic encephalopathy. BMJ Case Rep 2009; (2009) pii: bcr11.2008.1247
• 7 Pearl PL, Hyland K, Chiles J, McGavin CL, Yu Y, Taylor D. Partial pyridoxine responsiveness in PNPO deficiency. JIMD Rep 2013; 9: 139-142
• 8 Hoffmann GF, Schmitt B, Windfuhr M , et al. Pyridoxal 5′-phosphate may be curative in early-onset epileptic encephalopathy. J Inherit Metab Dis 2007; 30 (1) 96-99
• 9 Khayat M, Korman SH, Frankel P , et al. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. Mol Genet Metab 2008; 94 (4) 431-434
• 10 Schmitt B, Baumgartner M, Mills PB , et al. Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency. Dev Med Child Neurol 2010; 52 (7) e133-e142
• 11 Plecko B, Paul K, Paschke E , et al. PNPO mutations in patients with pyridoxine dependent epilepsy [Abstract]. Neuropediatrics 2013; 44 (2) :FV12_07 DOI: 10.1055/s-0033-1337721
• 12 Musayev FN, Di Salvo ML, Saavedra MA , et al. Molecular basis of reduced pyridoxine 5′-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder. J Biol Chem 2009; 284 (45) 30949-30956