Abstract
The aim of our study was to describe the clinical, electroencephalogram, molecular findings and the diagnostic and therapeutic flow-chart of children with pyridoxine-dependent epilepsies (PDEs). We performed a retrospective observational study on children with PDEs, diagnosed and followed-up in Italian Pediatric Departments. In each centre, the authors collected data from a cohort of children admitted for intractable seizures, responsive to pyridoxine administration and resistant to other anticonvulsant therapies. Data were retrospectively analysed from January 2016 to January 2017. Sixteen patients (13 males, and 3 females) were included. We found that 93.75% of patients underwent conventional anticonvulsant therapy before starting pyridoxine administration and 62.5% had ex-juvantibus diagnosis, as specific serum diagnostic tests had been performed in only 37.5% of patients by alpha-AASA and pipecolic acid blood and urine dosage. The most common type of seizure was generalized tonic-clonic in 7 patients and the most common EEG pattern was characterized by a “burst suppression” pattern. Before pyridoxine administration, other anticonvulsant drugs were used in 93.75% of patients, with consequent onset of drug-resistance. Phenobarbital was the most frequently used drug as first-line treatment. The importance of our study relies on the need of a deeper knowledge of PDEs in terms of early diagnosis, avoiding incorrect treatment and related adverse events, clinical and EEG pathognomonic features, and genetic aspects of the disease.
Similar content being viewed by others
References
Baxter P (1999) Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child 81(5):431–433. https://doi.org/10.1136/adc.81.5.431
Baxter P (2001) Pyridoxine-dependent and Pyridoxine-responsive seizures. Dev Med Child Neurol 43(06):416–420. https://doi.org/10.1017/S0012162201000779
Baxter P, Griffiths P, Kelly T, Gardner-Medwin D (1996) Pyridoxine-dependent seizures: demographic, clinical, MRI and psychometric features, and effect of dose on intelligence quotient. Dev Med Child Neurol 38(11):998–1006
Been JV, Bok LA, Andriessen P, Renier WO (2005) Epidemiology of pyridoxine dependent seizures in the Netherlands. Arch Dis Child 90(12):1293–1296. https://doi.org/10.1136/adc.2005.075069
Bennett CL, Chen Y, Hahn S, Glass IA, Gospe SM (2009) Prevalence of ALDH7A1 mutations in 18 north American pyridoxine-dependent seizure (PDS) patients. Epilepsia 50(5):1167–1175. https://doi.org/10.1111/j.1528-1167.2008.01816.x
Darin N, Reid E, Prunetti L, Samuelsson L, Husain RA, Wilson M, El Yacoubi B et al (2016) Mutations in PROSC disrupt cellular Pyridoxal phosphate homeostasis and cause vitamin-B6-dependent epilepsy. Am J Hum Genet 99(6):1325–1337. https://doi.org/10.1016/j.ajhg.2016.10.011
Ebinger M, Schultze C, König S (1999) Demographics and diagnosis of pyridoxine-dependent seizures. J Pediatr 134(6):795–796. https://doi.org/10.1016/S0022-3476(99)70307-0
Fujikawa Y, Sugai K, Hanaoka S, Fukumizu M, Sasaki M, Kaga M (2003) Three cases with severe motor and intellectual disabilities presenting the severest condition caused by prolonged non-convulsive status epilepticus. No To Hattatsu 35(1):43–48
Goutières F, Aicardi J (1985) Atypical presentations of pyridoxine-dependent seizures: a treatable cause of intractable epilepsy in infants. Ann Neurol 17(2):117–120. https://doi.org/10.1002/ana.410170203
Hunt A Jr, Stokes J Jr, Mccrory WW, Stroud HH (1954) Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics 13:140–145
Koul R (2009) Pyridoxine-dependent seizures: 10-year follow-up of eight cases. Neurol India 57(4):460–463. https://doi.org/10.4103/0028-3886.55595
Millis PB, Struys E, Jakobs C, Plaeko B, Baxter P, Baumgartner M et al (2006) Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 12(3):307–309. https://doi.org/10.1038/nm1366
Nabbout R, Soufflet C, Plouin P, Dulac O (1999) Pyridoxine dependent epilepsy: a suggestive electroclinical pattern. Arch Dis Child Fetal Neonatal Ed 81(2):F125–F129. https://doi.org/10.1136/fn.81.2.F125
Oliveira R, Pereira C, Rodrigues F, Alfaite C, Garcia P, Robalo C, Fineza I, Gonçalves O, Struys E, Salomons G, Jakobs C, Diogo L (2013) Pyridoxin-dependent epilepsy due to antiquitin deficiency: achieving a favourable outcome. Epileptic Disord 15(4):400–406. https://doi.org/10.1684/epd.2013.0610.
Plecko B, Paul K, Mills P, Clayton P, Paschke E, Maier O, Hasselmann O, Schmiedel G, Kanz S, Connolly M, Wolf N, Struys E, Stockler S, Abela L, Hofer D (2014) Pyridoxine responsiveness in novel mutations of the PNPO gene. Neurology 82(16):1425–1433. https://doi.org/10.1212/WNL.0000000000000344
Riis P (2000) Perspectives on the fifth revision of the declaration of Helsinki. JAMA 284(23):3045–3046. https://doi.org/10.1001/jama.284.23.3045
Salomons GS, Bok LA, Struys EA, Pope LL, Darmin PS, Mills PB, Clayton PT, Willemsen MA, Jakobs C (2007) An intriguing "silent" mutation and a founder effect in antiquitin (ALDH7A1). Ann Neurol 62(4):414–418. https://doi.org/10.1002/ana.21206
Schmitt B, Baumgartner M, Mills PB, Clayton PT, Jakobs C, Keller E et al (2010) Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency. Dev Med Child Neurol 52(7):e133–e142. https://doi.org/10.1111/j.1469-8749.2010.03660.x
Stockler S, Plecko B, Gospe SM Jr, Coulter-Mackie M, Connolly M, van Karnebeek C et al (2011) Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 104(1-2):48–60. https://doi.org/10.1016/j.ymgme.2011.05.014
Vitaliti G, Pavone P, Mahmood F, Nunnari G, Falsaperla R (2014) Targeting inflammation as a therapeutic strategy for drug-resistant epilepsies: an update of new immune-modulating approaches. Hum Vaccin Immunother 10(4):868–875. https://doi.org/10.4161/hv.28400
Xue J, Qian P, Li H, Wu Y, Liu X, Yang Z (2015) A cohort study of pyridoxine-dependent epilepsy and high prevalence of splice site IVS11+1G>A mutation in Chinese patients. Epilepsy Res 118:1–4. https://doi.org/10.1016/j.eplepsyres.2015.10.002.
Yeghiazaryan NS, Zara F, Capovilla G, Brigati G, Falsaperla R, Striano P (2012) Pyridoxine-dependent epilepsy: an under-recognised cause of intractable seizures. J Paediatr Child Health 48(3):E113–E115. https://doi.org/10.1111/j.1440-1754.2010.01866.x
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Conflict of interest
All authors declare not to present any conflict of interest in the publication of the present study.
Rights and permissions
About this article
Cite this article
Falsaperla, R., Vari, M.S., Toldo, I. et al. Pyridoxine-dependent epilepsies: an observational study on clinical, diagnostic, therapeutic and prognostic features in a pediatric cohort. Metab Brain Dis 33, 261–269 (2018). https://doi.org/10.1007/s11011-017-0150-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-017-0150-x