Pyridoxal phosphate-dependent neonatal epileptic encephalopathy

Bağcı, Soyhan; Zschocke, Johannes; Hoffmann, G. F.; Bast, Thomas; Klepper, Jörg; Müller, Andreas; Heep, Andrea; Bartmann, Peter; Franz, Axel R.

doi:10.1136/adc.2006.115162

Cited by 55 publications

(30 citation statements)

References 7 publications

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“…elevated serine, glycine (consequent of defective glycine cleavage system) and threonine (threonine dehydratase) and decreased 5-hydroxyindoleacetic acid and homovanillic acids with elevated 3-methoxytyrosine (due to decreased L-AADC function) (Goyal et al 2013;Clayton 2006). However, normality in these biochemical parameters cannot completely exclude PNPO deficiency, as patients have been reported with normal CSF amino acids and neurotransmitter values (Hoffmann et al 2007;Bagci et al 2008). Case 1 in our cohort supports this observation and highlights the importance of a clinical trial of PLP in neonates with encephalopathy.…”

Section: Discussionmentioning

confidence: 99%

“…The initial clinical reported phenotype of PNPO deficiency included prematurity, early-onset neonatal encephalopathy and seizures that are resistant to conventional anticonvulsants and pyridoxine. Those who have survived the neonatal period have had significant neurodevelopmental disorders in the form of ongoing seizures, developmental delay and microcephaly (Mills et al 2005;Hoffmann et al 2007;Bagci et al 2008;Ruiz et al 2008). As is often the case with rare diseases, the clinical phenotype expands as more cases are diagnosed with time.…”

Section: Pyridoxal-5mentioning

confidence: 99%

“…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: Discussionmentioning

confidence: 99%

Section: Pyridoxal-5mentioning

confidence: 99%

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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“…Vitamin B12-responsive methylmalonic aciduria can be treated by supplementation of the mother with high doses of vitamin B12 [1]. Finally, another defect of pyridoxine metabolism, namely pyridox(am)ine-5′-phosphate oxidase, should (at least theoretically) be treatable by supplementation of pyridoxal-5′-phosphate, the active form of pyridoxine [2]. The current study is limited by its retrospective nature and the small sample size, which is due to the rare nature of PDS.…”

Section: Discussionmentioning

confidence: 99%

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

et al. 2009

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Incidental reports suggest that antenatal treatment of pyridoxine dependent seizures (PDS) may improve neurodevelopmental outcome of affected patients. Two families with PDS are reported, both with two affected siblings. Antenatal treatment with pyridoxine was instituted during the second pregnancy in each family (50 and 60 mg daily from 3 and 10 weeks of gestation, respectively). Perinatal characteristics and neurodevelopmental outcome at 4 (Family A) and 12 (Family B) years of age were compared between the untreated and treated child within each family. Meconium-stained amniotic fluid was present in both first pregnancies and abnormal foetal movements were noticed in one. In the treated infants, pregnancy and birth were uncomplicated. In family A, postnatal pyridoxine supplementation prevented neonatal seizures. Both children in family A were hypotonic and started walking after 2 years of age; both had white matter changes on MRI, and the first child was treated for squint. IQ was 73 and 98 in the antenatally untreated and treated child, respectively. The second child in family B developed seizures on the seventh day, because pyridoxine maintenance therapy had not been instituted after birth. Seizures responded rapidly to pyridoxine supplementation. MRI showed large ventricles and a mega cisterna magna. IQ was 80 and 106 in the antenatally untreated and treated child respectively. Both children had normal motor development. These results suggest that antenatal pyridoxine supplementation may be effective in preventing intrauterine seizures, decreasing the risk of complicated birth and improving neurodevelopmental outcome in PDS.

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“…Mills and colleagues subsequently described the genotype and phenotype of neonatal epileptic encephalopathy due to pyridoxamine 5 0 -phosphate oxidase (PNPO) deficiency (Mills et al 2005). The treatment dose of PLP has largely been empirical, guided by clinical response with reported doses varying from 30 to 60 mg/kg/day (Mills et al 2005;Hoffmann et al 2007;Bagci et al 2008). PLP is not licensed as a drug for the treatment of epilepsy outside of Asia.…”

Section: Introductionmentioning

confidence: 99%

Cirrhosis Associated with Pyridoxal 5′-Phosphate Treatment of Pyridoxamine 5′-Phosphate Oxidase Deficiency

et al. 2014

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We report the case of an 8-year-old boy with pyridoxamine 5 0 -phosphate oxidase (PNPO) deficiency. He developed seizures at 24 h of age that were refractory to standard anticonvulsant therapy and a trial of pyridoxine but responded to pyridoxal phosphate (PLP) at 28 days of life. Genetic testing identified compound heterozygous mutations in the PNPO gene. Management of encephalopathic episodes required escalation of PLP dose to 100 mg/kg/day by 2 years of age. Routine blood tests at this time showed significantly deranged liver function tests (LFTs). A wedge liver biopsy showed early cirrhosis with marked elevation of pyridoxal and pyridoxic acid levels in the liver sample. Despite extensive investigation, no cause other than PLP therapy could be identified for the cirrhosis. The PLP dose was weaned to 50 mg/kg/day before episodes of encephalopathy recurred. Concurrent with the reduction of his PLP dose, LFTs showed improvement. However, at 8 years of age, there is persistent evidence of hepatic fibrosis and early portal hypertension. We hypothesise that hepatic toxicity due to PLP or its degradation products is the cause of cirrhosis in this boy. Until further evidence becomes available, we would suggest that people with PNPO deficiency are treated with the minimum dose of PLP required to prevent episodes of encephalopathy.

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Pyridoxal phosphate-dependent neonatal epileptic encephalopathy

Cited by 55 publications

References 7 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

Antenatal treatment in two Dutch families with pyridoxine-dependent seizures

Cirrhosis Associated with Pyridoxal 5′-Phosphate Treatment of Pyridoxamine 5′-Phosphate Oxidase Deficiency

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