Pyridoxine responsiveness in novel mutations of the
            <i>PNPO</i>
            gene

Plecko, Barbara; Paul, K. B.; Mills, Philippa B.; Clayton, Peter T.; Paschke, Eduard; Maier, Oliver; Hasselmann, Oswald; Schmiedel, G.; Kanz, Simone; Connolly, Mary; Wolf, Nicole I.; Struys, Eduard A.; Stöckler, Sylvia; Abela, Lucia; Hofer, Doris

doi:10.1212/wnl.0000000000000344

Cited by 92 publications

(110 citation statements)

References 27 publications

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“…Early diagnosis and treatment with PLP have been linked with improved neurodevelopmental outcomes (Hoffmann et al 2007;Plecko et al 2014) with more recent reports supporting that normal neurodevelopmental outcomes can occur (Khayat et al 2008;Mills et al 2014;Plecko et al 2014). The four cases reported in this paper reinforce these observations, with case 2 being the only known patient to have been treated as a preventative measure from birth, until it was confirmed by genetic testing whether she had PNPO deficiency or otherwise.…”

Section: Discussionsupporting

confidence: 74%

“…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.…”

Section: Pyridoxal-5mentioning

confidence: 99%

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

Hatch

Coman

Clayton³

et al. 2015

JIMD Reports

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Pyridox(am)ine 5 0 -phosphate oxidase deficiency results in an early-onset neonatal encephalopathy that can be fatal if not detected and treated early. The condition is rare, can result in preterm delivery, and can mimic hypoxic ischemic encephalopathy. Thus, suspicion of the diagnosis, appropriate investigations, and therapeutic trials with pyridoxal-5 0 -phosphate are often delayed. In this paper we report four cases of pyridox(am)ine 5 0 -phosphate oxidase deficiency, two of whom are siblings. Three were treated with pyridoxal-5 0 -phosphate in the first few days of life and the fourth within the first month. One of the siblings was electively treated from birth until a diagnosis was secured. Our cases demonstrate that early diagnosis and treatment can be associated with normal neurodevelopment in childhood. We suggest that a low threshold for investigating for pyridox(am)ine 5 0 -phosphate oxidase deficiency and electively treating with pyridoxal-5 0 -phosphate is considered in any neonate with encephalopathy, including those with presumed hypoxic ischemic encephalopathy in whom the degree of encephalopathy is not expected from perinatal history, cord gases and/or neuroimaging.

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Section: Discussionsupporting

confidence: 74%

Section: Pyridoxal-5mentioning

confidence: 99%

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

Hatch

Coman

Clayton³

et al. 2015

JIMD Reports

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“…PLP-responsive epilepsy is highly correlated with the incidence of prematurity Plecko et al, 2014). Seizures resulting from PNPO deficiency typically occur in utero, or shortly after birth, with various, ictal manifestations predominantly multifocal and generalized myoclonic seizures that are refractory to conventional anticonvulsants and pyridoxine.…”

Section: Discussionmentioning

confidence: 99%

“…Various clinical courses and outcomes have been reported in previous cases of PNPO deficiency (Plecko, 2013;Plecko et al, 2014). If left untreated, the patients can develop failure to thrive, refractory seizures, and severe encephalopathy, leading to early death.…”

Section: Discussionmentioning

confidence: 99%

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

Veeravigrom¹,

Damrongphol²,

Ittiwut³

et al. 2015

Genet. Mol. Res.

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“…If abnormal, DNA sequencing of the pyridoxal 59-phosphate oxidase gene can be performed. 19 Although PDE is rare, it is a potentially treatable cause of neonatal-onset epilepsy that should be aggressively and systematically evaluated for the best possible outcome. PDE also can have later-onset presentation (beyond neonatal and infancy periods) and testing for this condition should be considered in older children with intractable epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy

et al. 2015

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Pyridoxine-dependent epilepsy is a rare, autosomal recessive, treatable cause of neonatal seizures. Genetic testing can confirm mutations in the ALDH7A1 gene, which encodes antiquitin. To avoid delays in initiating treatment while awaiting confirmatory genetic testing, it is recommended that all neonates with unexplained seizures should receive trial of intravenous (IV) pyridoxine to assess for responsiveness. However, oral pyridoxine is not commonly continued in the absence of the typical EEG changes. Two cases are presented that highlight the potential inadequacy of this single-step approach. One neonate ultimately diagnosed with pyridoxine-dependent seizures had no EEG changes after administration of IV pyridoxine. In contrast, another neonate who did not have this diagnosis had profound EEG changes after pyridoxine administration. We present 2 cases that highlight the difficulties in using initial EEG response to IV pyridoxine in establishing a diagnosis of pyridoxine-dependent seizures in the neonate. Given the availability of biochemical markers and gene testing, we suggest that oral pyridoxine treatment should be continued until biochemical and/or genetic testing has confirmed the presence or absence of pyridoxine-dependent epilepsy.

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Pyridoxine responsiveness in novel mutations of the PNPO gene

Abstract: Objective: To determine whether patients with pyridoxine-responsive seizures but normal biomarkers for antiquitin deficiency and normal sequencing of the ALDH7A1 gene may have PNPO mutations. Methods:We sequenced the PNPO gene in 31 patients who fulfilled the above-mentioned criteria.

Cited by 92 publications

References 27 publications

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

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

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

Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy

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