Partial Pyridoxine Responsiveness in PNPO Deficiency

Pearl, Phillip L.; Hyland, Keith; Chiles, Jessica; McGavin, Colleen L.; Yu, Yuezhou; Taylor, D. C.

doi:10.1007/8904_2012_194

Cited by 38 publications

(49 citation statements)

References 8 publications

(4 reference statements)

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“…Neonatal encephalopathies are uncommon, with an incidence of 9 in 1,000 live births worldwide (Graham et al 2008 (Mills et al 2005;Schmitt et al 2010), (2) burst suppression EEG pattern (Veerapandiyan et al 2011), (3) non-responsiveness to pyridoxine (Clayton 2006), (4) complete or partial responsiveness to PLP (Pearl et al 2013), (5) prematurity (Veerapandiyan et al 2011) and (6) neonatal lethality if the diagnosis is not suspected and PLP administered (Khayat et al 2008). 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).…”

Section: Discussionmentioning

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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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%

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

Hatch

Coman

Clayton³

et al. 2015

JIMD Reports

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“…In the 24 patients with PNPO deficiency harboring a total of 10 different mutations published to date, 1,[3][4][5][6][8][9][10] only 2 have shown a partial pyridoxine response with improvement when switched to PLP. 1,8 In contrast, all 9 patients harboring specific novel PNPO mutations published in this article had partial or even complete pyridoxine response and were thus initially suspected to have antiquitin deficiency by their referring physician. Antiquitin deficiency was excluded by normal AASA or PA concentrations in all families and by wild-type sequence of the ALDH7A1 gene in every living patient.…”

Section: Expression Studies In Cho-k1 Cell Lines (Laboratory Ofmentioning

confidence: 99%

Pyridoxine responsiveness in novel mutations of the PNPO gene

et al. 2014

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“…More recently, defects in both the quantity and functional configuration of PNPO have also been identified in children with early epileptic encephalopathies. 3–7 Children with PNPO deficiency require treatment with P5P to circumvent the need for conversion of pyridoxine to P5P Mills et al 8 ; however, some may have a partial response to pyridoxine Pearl et al 3–5,9 …”

Section: Introductionmentioning

confidence: 99%

Systemic Manifestations in Pyridox(am)ine 5′-Phosphate Oxidase Deficiency

Guerriero

Patel

Walsh

et al. 2017

Pediatric Neurology

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OBJECTIVE Pyridoxine is converted to its biologically active form pyridoxal-5-phosphate (P5P) by the enzyme pyridox(am)ine 5′-phosphate oxidase and serves as a cofactor in nearly 200 reactions in the central nervous system. Pyridox(am)ine 5′-phosphate oxidase deficiency leads to P5P dependent epilepsy, typically a neonatal- or infantile-onset epileptic encephalopathy treatable with P5P or in some cases, pyridoxine. Following identification of retinopathy in a patient with pyridox(am)ine 5′-phosphate oxidase deficiency that was reversible with P5P therapy, we describe the systemic manifestations of pyridox(am)ine 5′-phosphate oxidase deficiency. METHODS A series of six patients with homozygous mutations of PNPO, the gene coding pyridox(am)ine 5′-phosphate oxidase, were evaluated in our center over the course of two years for phenotyping of neurological and systemic manifestations. RESULTS Five of six were born prematurely, three had anemia and failure to thrive, and two had elevated alkaline phosphatase. A movement disorder was observed in two children, and a reversible retinopathy was observed in the most severely affected infant. All patients had neonatal-onset epilepsy and were on a continuum of developmental delay to profound encephalopathy. Electroencephalographic features included background slowing and disorganization, absent sleep features, and multifocal and generalized epileptiform discharges. All the affected probands carried a homozygous PNPO mutation (c.674 G>T, c.686 G>A and c.352G>A). CONCLUSION In addition to the well-described epileptic encephalopathy, pyridox(am)ine 5′-phosphate oxidase deficiency causes a range of neurological and systemic manifestations. A movement disorder, developmental delay, and encephalopathy, as well as retinopathy, anemia, and failure to thrive add to the broadening clinical spectrum of P5P dependent epilepsy.

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Partial Pyridoxine Responsiveness in PNPO Deficiency

Cited by 38 publications

References 8 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

Pyridoxine responsiveness in novel mutations of the PNPO gene

Systemic Manifestations in Pyridox(am)ine 5′-Phosphate Oxidase Deficiency

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