title: Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The PDE Consortium Consensus Recommendations.
abstract: BACKGROUND
  Seventy-five percent of patients with pyridoxine-dependent epilepsy (PDE) due to Antiquitin (ATQ) deficiency suffer from developmental delay and/or intellectual disability (IQ < 70) despite seizure control. An observational study showed that adjunct treatment with a lysine-restricted diet is safe, results in partial normalization of lysine intermediates in body fluids, and may have beneficial effects on seizure control and psychomotor development.
  
  
  METHODS
  In analogy to the NICE guideline process, the international PDE Consortium, an open platform uniting scientists and clinicians working in the field of this metabolic epilepsy, during four workshops (2010-2013) developed a recommendation for a lysine-restricted diet in PDE, with the aim of standardizing its implementation and monitoring of patients. Additionally, a proposal for a further observational study is suggested.
  
  
  RESULTS
  (1) All patients with confirmed ATQ deficiency are eligible for adjunct treatment with lysine-restricted diet, unless treatment with pyridoxine alone has resulted in complete symptom resolution, including normal behavior and development. (2) Lysine restriction should be started as early as possible; the optimal duration remains undetermined. (3) The diet should be implemented and the patient be monitored according to these recommendations in order to assure best possible quality of care and safety.
  
  
  CONCLUSIONS
  The implementation of this recommendation will provide a unique and a much needed opportunity to gather data with which to refine the recommendation as well as improve our understanding of outcomes of individuals affected by this rare disease. We therefore propose an international observational study that would utilize freely accessible, online data sharing technologies to generate more evidence.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, 3091-950 West 28th Avenue, Vancouver, Canada, V5Z 4H4, cvankarnebeek@cw.bc.ca.
authors.forename: Clara D M
authors.initials: CD
authors.lastname: van Karnebeek
authors.forename: Sylvia
authors.initials: S
authors.lastname: Stockler-Ipsiroglu
authors.forename: Sravan
authors.initials: S
authors.lastname: Jaggumantri
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmann
authors.forename: Peter
authors.initials: P
authors.lastname: Baxter
authors.forename: Daniela
authors.initials: D
authors.lastname: Buhas
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Bok
authors.forename: Barbara
authors.initials: B
authors.lastname: Cheng
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Coughlin
authors.forename: Anibh M
authors.initials: AM
authors.lastname: Das
authors.forename: Alette
authors.initials: A
authors.lastname: Giezen
authors.forename: Wahla
authors.initials: W
authors.lastname: Al-Hertani
authors.forename: Gloria
authors.initials: G
authors.lastname: Ho
authors.forename: Uta
authors.initials: U
authors.lastname: Meyer
authors.forename: Philippa
authors.initials: P
authors.lastname: Mills
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.forename: Eduard
authors.initials: E
authors.lastname: Struys
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
authors.forename: Monique
authors.initials: M
authors.lastname: Albersen
authors.forename: Nanda
authors.initials: N
authors.lastname: Verhoeven
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Gospe
authors.forename: Renata C
authors.initials: RC
authors.lastname: Gallagher
authors.forename: Johan K L
authors.initials: JK
authors.lastname: Van Hove
authors.forename: Hans
authors.initials: H
authors.lastname: Hartmann
references.citation: Dev Med Child Neurol. 2012 Sep;54(9):849-54
references.pmid: 22804844
references.citation: Ann Neurol. 2014 Jan;75(1):22-32
references.pmid: 24122892
references.citation: Br J Nutr. 1999 Jan;81(1):7-20
references.pmid: 10341670
references.citation: Eur J Pediatr. 1991 May;150(7):452-5
references.pmid: 1915493
references.citation: J Inherit Metab Dis. 2013 Jan;36(1):139-45
references.pmid: 22576361
references.citation: Eur J Pediatr. 2009 Jun;168(6):697-704
references.pmid: 18762976
references.citation: Brain. 2010 Jul;133(Pt 7):2148-59
references.pmid: 20554659
references.citation: Eur Rev Med Pharmacol Sci. 2012 May;16(5):695-8
references.pmid: 22774414
references.citation: Pediatr Res. 2006 Jun;59(6):840-7
references.pmid: 16641220
references.citation: J Inherit Metab Dis. 2011 Jun;34(3):677-94
references.pmid: 21431622
references.citation: Mol Genet Metab. 2011 Sep-Oct;104(1-2):48-60
references.pmid: 21704546
references.citation: Mol Genet Metab. 2012 Sep;107(1-2):72-80
references.pmid: 22520952
references.citation: J Inherit Metab Dis. 2012 Nov;35(6):1031-6
references.pmid: 22403017
references.citation: World Health Organ Tech Rep Ser. 1985;724:1-206
references.pmid: 3937340
references.citation: Mol Genet Metab. 2013 Sep-Oct;110(1-2):197
references.pmid: 23683770
references.citation: Mol Genet Metab. 2011 Sep-Oct;104(1-2):93-106
references.pmid: 21820344
references.citation: Ann Neurol. 2010 Nov;68(5):743-52
references.pmid: 21031586
references.citation: Mol Genet Metab. 2012 Nov;107(3):335-44
references.pmid: 23022070
references.citation: Nat Med. 2006 Mar;12(3):307-9
references.pmid: 16491085
references.citation: Mol Genet Metab. 2013 Nov;110(3):237-40
references.pmid: 23953072
references.citation: Arch Dis Child Fetal Neonatal Ed. 1999 Sep;81(2):F125-9
references.pmid: 10448181
references.citation: J Inherit Metab Dis. 2012 Nov;35(6):1147-52
references.pmid: 22358739
references.citation: Dev Med Child Neurol. 2012 Sep;54(9):781-2
references.pmid: 22803601
references.citation: Dev Med Child Neurol. 2001 Jun;43(6):416-20
references.pmid: 11409832