Electroencephalographic and seizure manifestations of pyridoxal 5′-phosphate-dependent epilepsy

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

“…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).…”

“…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.…”

Pyridoxine responsiveness in novel mutations of the PNPO gene

“…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.…”

“…[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.…”

Genetics of Pediatric Epilepsy

“…In such situations, genetic testing is justifiable because the yield is relatively high (as high as 34.5%) and there is more of a chance of uncovering potentially treatable genetic conditions, such as vitamin-responsive genetic epilepsies. [21][22][23][24][25][26][27] Genetic testing in patients with intractable epilepsy and developmental delay usually involves, in addition to metabolic testing for inborn errors of metabolism and vitamin dependent conditions, 1 or more of the following: karyotype, chromosomal microarray, specific gene or gene panel sequencing, or whole exome sequencing. This testing often leads to closure of the search for an underlying etiology and helps physicians to better prognosticate and families to better accept and deal with the problem.…”