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.

Pyridoxine responsiveness in novel mutations of the PNPO gene

“…This seems paradoxical but has so far been reported in 3 other patients with PNPO deficiency. 4,6,15 Elevation of urinary vanillactate due to the buildup of L-dopa is present in about 80% of PNPO patients and has been raised in the one patient from this series who underwent determination. Recently, distinct B 6 vitamer profiles have been described in the plasma of patients with PNPO deficiency, even when on treatment.…”

“…[12][13][14] Complete seizure freedom or occasional seizures on PLP monotherapy have so far been reported in single patients with PNPO deficiency. 10,14,15 Of interest, in our cohort of patients with pyridoxine-responsive PNPO mutations, 6 patients (66%) were completely seizure-free on pyridoxine Table 3 Mutation analysis of the PNPO gene in 11 patients from 7 unrelated families: Reference sequence NM_018129 monotherapy, in some with only 2 single doses a day. Still, these pyridoxine-responsive PNPO mutations cannot be regarded as "mild," as 2 siblings have died from epileptic encephalopathy in the absence of continuous pyridoxine treatment and 2 patients with treatment delay are severely handicapped.…”

Normal Neurodevelopmental Outcomes in PNPO Deficiency: A Case Series and Literature Review

“…To date there have been <40 cases reported in the medical literature (Mills et al 2005Hoffmann et al 2007;Bagci et al 2008;Ruiz et al 2008;Schmitt et al 2010;Veerapandiyan et al 2011;Ware et al 2014;Plecko et al 2014;Porri et al 2014). The initial clinical reported phenotype of PNPO deficiency included prematurity, early-onset neonatal encephalopathy and seizures that are resistant to conventional anticonvulsants and pyridoxine.…”

Pyridoxal 5ꞌ-phosphate-responsive epilepsy with novel mutations in the PNPO gene: a case report

“…If left untreated, the patients can develop failure to thrive, refractory seizures, and severe encephalopathy, leading to early death. Patients in whom the disease was recognized early, and who received appropriate treatment are believed to be more likely to have favorable outcomes (Hoffmann et al, 2007;Porri et al, 2014). This was supported by the results of a previous study describing a male infant with a homozygous splice-site mutation in the PNPO gene.…”

“…This was supported by the results of a previous study describing a male infant with a homozygous splice-site mutation in the PNPO gene. The patient had seizures within 12 h after birth, and received PLP treatment on day 3; a favorable neurological outcome was observed at the age of 3 months (Porri et al, 2014). Delay in PLP treatment usually leads to motor and intellectual disabilities.…”