Selected Scientific Papers Concerning
Pyridoxine-Dependent Seizures

Comprehensive Web-Based Review:

Gospe SM, Jr. Pyridoxine-dependent epilepsy, In: Pagon, RA, Adam, MP, Ardinger, HH, Wallace, SE, Amemiya, A, Bean, LJH, et al. editors, GeneReviews © 1993-2015 [Internet]. University of Washington, Seattle. Available at:

General Review Papers:

Baxter P. Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol. 2001;43:416-420.

Baxter P. Pyridoxine-dependent seizures: a clinical and biochemical conundrum. Biochim Biopphys Acta. 2003;1647:36-41. Abstract

Gospe SM, Jr. Current perspectives on pyridoxine-dependent seizures. J Pediatr. 1998;132:919-23. Abstract

Gospe SM, Jr. Neonatal vitamin-responsive epileptic encephalopathies. Chang Gung Med J. 2010;33(1):1-12. Abstract pdf available at:

Gospe SM, Jr. Pyridoxine-dependent seizures: findings from recent studies pose new questions. Pediatr Neurol. 2002;26:181-185. Abstract

Gospe SM, Jr. Pyridoxine-dependent seizures: new genetic and biochemical clues to help with diagnosis and treatment. Curr Opin Neurol. 2006;19:148-153. Abstract

Haenggeli C-A, Girardin E, Paunier L. Pyridoxine-dependent seizures, clinical and therapeutic aspects. Eur J Pediatr. 1991;150:452-5. Abstract

Stockler, S, Plecko, B, Gospe, SM, Jr, Coulter-Mackie, M, Connolly, M, van Karnebeek, C, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab 2011;104:48-60. Abstract

Clinical Descriptions, Demographics and Case Reports:

Bankier A, Turner M, Hopkins IJ. Pyridoxine dependent seizures--a wider clinical spectrum.Arch Dis Child. 1983;58:415-8. Abstract

Baxter P, Griffiths P, Kelly T, Gardner-Medwin D. Pyridoxine-dependent seizures: demographic, clinical, MRI and psychometric features, and effect of dose on intelligence quotient. Dev Med Child Neurol. 1996;38:998-1006. Abstract

Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child. 1999;81:431-3. Abstract

Baynes K, Farias ST, Gospe SM Jr. Pyridoxine-dependent seizures and cognition in adulthood. Dev Med Child Neurol. 2003;45:782-5. Abstract

Been JV, Bok JA, Andriessen P, Renier WO. Epidemiology of pyridoxine-dependent seizures in The Netherlands. Arch Dis Child. 2005;90:1293-6. Abstract

Coker SB. Postneonatal vitamin B6-dependent epilepsy. Pediatrics. 1992;90:221-3. Abstract

Ebinger M, Schutze C, Konig S. Demographics and diagnosis of pyridoxine-dependent seizures. J Pediatr. 1999;134:795-6.

Goutières F, Aicardi J. Atypical presentations of pyridoxine-dependent seizures: a treatable cause of intractable epilepsy in infants. Ann Neurol. 1985;17:117-20. Abstract

Hunt AD, Stokes J, McCrory WW, Stroud HH. Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics. 1954;13:140-5.

Kluger G, Blank R, Paul K, Paschke E, Jansen E, Jakobs C, et al. Pyridoxine-dependent epilepsy: normal outcome in a patient with late diagnosis after prolonged status epilepticus causing cortical blindness. Neuropediatrics. 2008;39:276-9. Abstract

Ohtsuka Y, Hattori J, Ishida T, Ogino T, Oka E. Long-term follow-up of an individual with vitamin B6-dependent seizures. Dev Med Child Neurol. 1999;41:203-6. Abstract

Risks of Pyridoxine:

Bass NE, Wyllie E, Cohen B, Joseph SA Pyridoxine-dependent epilepsy: the need for repeated pyridoxine trials and the risk of severe electrocerebral suppression with intravenous pyridoxine infusion. J Child Neurol. 1996;11:422-4. Abstract

Kroll JS. Pyridoxine for neonatal seizures: an unexpected danger. Dev Med Child Neurol. 1985;27:377-9. Abstract

McLachlan RS, Brown WF. Pyridoxine dependent epilepsy with iatrogenic sensory neuronopathy. Can J Neurol Sci. 1995;22:50-1. Abstract

EEG Findings:

Bok LA, Maurits NM, Willemsen MA, Jakobs C, Teune LK, Poll-The BT, et al. The EEG response to pyridoxine-IV neither identifies nor excludes pyridoxine-dependent epilepsy. Epilepsia. 2010;51:2406-11. Abstract

Mikati MA, Trevathan E, Krishnamoorthy KS, Lombroso CT. Pyridoxine-dependent epilepsy: EEG investigation and long-term follow-up. Electroencephalogr Clin Neurophysiol. 1991;78:215-21. Abstract

Nabbout R; Soufflet C; Plouin P; Dulac O. Pyridoxine dependent epilepsy: a suggestive electroclinical pattern. Arch Dis Child Fetal Neonatal Ed. 1999;81:F125-9. Abstract

Naasan G, Yabroudi M, Rahi A, Mikati MA. Electroencephalographic changes in pyridoxine-dependant epilepsy: new observations. Epileptic Disord. 2009;11:293-300. Abstract

Schmitt B, Baumgartner M, Mills PB, Clayton PT, Jakobs C, Keller E, et al. Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine-dependent epilepsy and pyridoxine phosphate oxidase deficiency. Dev Med Child Neurol. 2010;52:e133-42. Abstract

Imaging Findings:

Friedman, SD, Ishak, GE, Poliachik, SL, Poliakov, AV, Otto, RK, Shaw, DW, et al. Callosal alterations in pyridoxine-dependent epilepsy. Dev Med Child Neurol 2014;56:1106-110. Abstract

Gospe SM, Jr., Hecht ST. Longitudinal MRI findings in pyridoxine-dependent seizures. Neurology. 1998;51:74-8. Abstract

Jain-Ghai, S, Mishra, N, Hahn, C, Blaser, S, Mercimek-Mahmutoglu, S. Fetal onset ventriculomegaly and subependymal cysts in a pyridoxine-dependent epilepsy patient. Pediatrics 2014;133:e10921096. Abstract

Jardim LB, Pires RF, Martins CE, Vargas CR, Vizioli J, Kliemann FA, Giugliani R. Pyridoxine-dependent seizures associated with white matter abnormalities. Neuropediatrics. 1994;25:259-61. Abstract

Shih JJ, Kornblum H, Shewmon DA. Global brain dysfunction inan infant with pyridoxine dependency: evaluation with EEG, evoked potentials, MRI, and PET. Neurology. 1996;47:824-6. Abstract

Tanaka R, Okumura M, Arima J, Yamakura S, Momoi T. Pyridoxine-dependent seizures: report of a case with atypical clinical features and abnormal MRI scans. J Child Neurol. 1992;7:24-8. Abstract

Biochemistry, Genetics and Neurobiology:

Baumeister FAM, Gsell W, Shin YS, Egger J. Glutamate in pyridoxine-dependent epilepsy: neurotoxic glutamate concentration in the cerebrospinal fluid and its normalization by pyridoxine. Pediatrics. 1994;94:318-21. Abstract

Battaglioli G, Rosen DR, Gospe SM, Jr., Martin DL. Glutamate decarboxylase is not genetically linked to pyridoxine-dependent seizures. Neurology. 2000;55:309-311. Abstract

Bennett CL, Chen Y, Hahn S, Glass IA, Gospe SM, Jr. Prevalence of ALDH7A1 mutations in 18 North American pyridoxine-dependent seizure (PDS) patients. Epilepsia. 2009;50:1167-75. Abstract

Bennett CL, Huynh HM, Chance PF, Glass IA, Gospe SM, Jr. Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures. Neurogenetics. 2005;6:143-9. Abstract

Bok LA, Struys E, Willemsen MA, Been JV, Jakobs C. Pyridoxine-dependent seizures in Dutch patients: diagnosis by elevated urinary alpha-aminoadipic semialdehyde levels. Arch Dis Child. 2007 Aug;92(8):687-9. Epub 2006 Nov 6. Abstract

Cormier-Daire V, Dagoneau N, Nabbout R, Burglen L, Penet C, Soufflet C, Desguerre I, Munnich A, Dulac O. A gene for pyridxoine-dependent epilepsy maps to chromosome 5q31. Am J Hum Genet. 2000;67:991-993. Abstract

Gallagher RC, Van Hove JL, Scharer G, Hyland K, Plecko B, Waters PJ, et al. Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol. 2009;65:550-6. Abstract

Gospe SM Jr, Olin KL, Keen CL. Reduced GABA synthesis in pyridoxine-dependent seizures.Lancet. 1994;343:1133-4. Abstract

Jansen, LA, Hevner, RF, Roden, WH, Hahn, SH, Jung, S, Gospe, SM, Jr. Glial localization of antiqutin: implications for pyridoxine-dependent epilepsy. Ann Neurol 2014;75:22-32. Abstract

Jung, S, Tran, NT, Gospe, SM, Jr, Hahn, SH. Preliminary investigation of the use of newborn dried blood spots in screening pyridoxine-dependent epilepsy by LC-MS/MS. Mol Genet Metab 2013;110:237-240. Abstract

Kanno J, Kure S, Narisawa A, Kamada F, Takayanagi M, Yamamoto K, Hoshino H, Goto T, Takahashi T, Haginoya K, Tsuchiya S, Baumeister FA, Hasegawa Y, Aoki Y, Yamaguchi S, Matsubara Y. Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis. Mol Genet Metab. 2007 Aug;91(4):384-9. Epub 2007 Apr 11. Abstract

Kurlemann G, Loscher W, Dominick HC, Palm GD. Disappearance of neonatal seizures and low CSF GABA levels after treatment with vitamin B6. Epilepsy Res. 1987;1:152-4. Abstract

Kurlemann G, Ziegler R, Gruneberg M, Bomelburg T, Ullrich K, Palm DG. Disturbance of GABA metabolism in pyridoxine-dependent seizures. Neuropediatrics. 1992;23:257-9. Abstract

Kure S, Maeda T, Fukushima N, Ohura T, Takahashi K, Nishikawa T, Matsubara Y, Izumi T, Narisawa K. A subtype of pyridoxine-dependent epilepsy with normal CSF glutamate concentration. J Inherit Metab Dis. 1998;21:431-2. Abstract

Kure S, Sakata Y, Miyabayashi S, Takahashi K, Shinka T, Matsubara Y, Hoshino H, Narisawa K. Mutation and polymorphic marker analyses of 65K- and 67K-glutamate decarboxylase genes in two families with pyridoxine-dependent epilepsy. J Hum Genet. 1998;43:128-31. Abstract

Lott IT, Coulombe T, Di Paolo RV, Richardson EP Jr, Levy HL. Vitamin B6-dependent seizures: pathology and chemical findings in brain. Neurology. 1978;28:47-54. Abstract

Mills PB, Footitt EJ, Mills KA, Tuschl K, Aylett S, Varadkar S, et al. Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency). Brain. 2010;133:2148-59. Abstract

Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nature Medicine. 2006;12:307-9. Abstract

Pérez, B, Gutiérrez, Solana, LG, Verdú, A, Merinero, B, Yuste-Checa, P, Tuiz-Sala, P, et al. Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option. Epilepsia 2013;54:239-48. Abstract

Plecko B, Hikel, C, Korenke, GC, Schmitt, B, Baumgartner M, Baumeister F, Jakobs C, Struys E, Erwa W, Stockler-Ipsiroglu S. Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics. 2005;36:200-5. Abstract

Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, Hartmann H, Luecke T, di Capua M, Korenke C, Hikel C, Reutershahn E, Freilinger M, Baumeister F, Bosch F, Erwa W. Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Hum Mutat. 2007 Jan;28(1):19-26. Abstract

Plecko B, Paul K, Paschke E, Stoeckler-Ipsiroglu S, Struys E, Jakobs C, et al. Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene. Hum Mutat. 2007;28:19-26. Abstract

Plecko B, Stockler-Ipsiroglu S, Paschke E, Erwa W, Struys E, Jakobs C. Pipecolic acid elevation in plasma and ceregrospinal fluid of two patients with pyridoxine-dependent epilepsy. Ann Neurol. 2000;48:121-5. Abstract

Rankin PM, Harrison S, Chong WK, Boyd S, Aylett SE. Pyridoxine-dependent seizures: a family phenotype that leads to severe cognitive deficits, regardless of treatment regime. Dev Med Child Neurol. 2007 Apr;49(4):300-5. Abstract

Sadilkova K, Gospe SM, Jr., Hahn SH. Simultaneous determination of alpha-aminoadipic semialdehyde, piperideine-6-carboxylate and pipecolic acid by LC-MS/MS for pyridoxine-dependent seizures and folinic acid-responsive seizures. J Neurosci Methods. 2009;184:136-41. Abstract

Salomons GS, Bok LA, Struys EA, Pope LL, Darmin PS, Mills PB, Clayton PT, Willemsen MA, Jakobs C. An intriguing "silent" mutation and a founder effect in antiquitin (ALDH7A1). Ann Neurol. 2007 Oct;62(4):414-8. Abstract

Scharer G, Brocker C, Vasiliou V, Creadon-Swindell G, Gallagher RC, Spector E, et al. The genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy due to mutations in ALDH7A1. J Inherit Metab Dis. 2010;33:571-81 Abstract

Segal EB, Grinspan ZM, Mandel AM, Gospe SM, Jr. Biomarkers aiding diagnosis of atypical presentation of pyridoxine-dependent epilepsy. Pediatr Neurol. 2011;44:289-91. Abstract

Yoshida T, Tada K, Arakawa T. Vitamin B 6 -dependency of glutamic acid decarboxylase in the kidney from a patient with vitamin B 6 dependent convulsion. Tohoku J Exp Med. 1971;104:195-8. Abstract

Dietary Managment

Mercimek-Mahmutoglu, S, Codeiro, D, Cruz, V, Hyland, K, Struys, EA, Kyriakopoulou, L, Mamak, E. Novel therapy for pyridoxine dependent epilepsy, due to ALDH7A2 genetic defect: L-arginine supplementation alternative to lysine-restricted diet. Eur J Paediatr Neurol 2014;18:741-746. Abstract

van Karnebeek, CD, Hartmann, H., Jaggumantri, S, Bok, LA, Cheng, B, Connolly, M, et al. Lysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials. Mol Genet Metab 2012;107:335-344. Abstract

van Karnebeek, CD, Stockler-Ipsiroglu, S, Jaggumantri, S, Assmann, B, Baxter, P, Bok LA, et al. Lysine-restricted diet as adjunct therapy for pyridoxine-dependent epilepsy: The PDE Consortium consensus recommendations. JIMD Rep 2014;15:1-11. Abstract