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. DISCUSSION: 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.
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. DISCUSSION: 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: Jana Heringer; S P Nikolas Boy; Regina Ensenauer; Birgit Assmann; Johannes Zschocke; Inga Harting; Thomas Lücke; Esther M Maier; Chris Mühlhausen; Gisela Haege; Georg F Hoffmann; Peter Burgard; Stefan Kölker Journal: Ann Neurol Date: 2010-11 Impact factor: 10.422
Authors: Laura A Jansen; Robert F Hevner; William H Roden; Si Houn Hahn; Sunhee Jung; Sidney M Gospe Journal: Ann Neurol Date: 2014-01-02 Impact factor: 10.422
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Authors: Clara D M van Karnebeek; Hans Hartmann; Sravan Jaggumantri; Levinus A Bok; Barb Cheng; Mary Connolly; Curtis R Coughlin; Anibh M Das; Sidney M Gospe; Cornelis Jakobs; Johanna H van der Lee; Saadet Mercimek-Mahmutoglu; Uta Meyer; Eduard Struys; Graham Sinclair; Johan Van Hove; Jean-Paul Collet; Barbara R Plecko; Sylvia Stockler Journal: Mol Genet Metab Date: 2012-09-10 Impact factor: 4.797
Authors: Stefan Kölker; S P Nikolas Boy; Jana Heringer; Edith Müller; Esther M Maier; Regina Ensenauer; Chris Mühlhausen; Andrea Schlune; Cheryl R Greenberg; David M Koeller; Georg F Hoffmann; Gisela Haege; Peter Burgard Journal: Mol Genet Metab Date: 2012-04-04 Impact factor: 4.797
Authors: Philippa B Mills; Emma J Footitt; Kevin A Mills; Karin Tuschl; Sarah Aylett; Sophia Varadkar; Cheryl Hemingway; Neil Marlow; Janet Rennie; Peter Baxter; Olivier Dulac; Rima Nabbout; William J Craigen; Bernhard Schmitt; François Feillet; Ernst Christensen; Pascale De Lonlay; Mike G Pike; M Imelda Hughes; Eduard A Struys; Cornelis Jakobs; Sameer M Zuberi; Peter T Clayton Journal: Brain Date: 2010-06-16 Impact factor: 13.501
Authors: Emma J Footitt; Peter T Clayton; Kevin Mills; Simon J Heales; Viruna Neergheen; Marcus Oppenheim; Philippa B Mills Journal: J Inherit Metab Dis Date: 2012-05-11 Impact factor: 4.982
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Authors: Amal Al Teneiji; Theodora U J Bruun; Dawn Cordeiro; Jaina Patel; Michal Inbar-Feigenberg; Shelly Weiss; Eduard Struys; Saadet Mercimek-Mahmutoglu Journal: Metab Brain Dis Date: 2016-11-23 Impact factor: 3.584
Authors: Hilal H Al-Shekaili; Terri L Petkau; Izabella Pena; Tess C Lengyell; Nanda M Verhoeven-Duif; Jolita Ciapaite; Marjolein Bosma; Martijn van Faassen; Ido P Kema; Gabriella Horvath; Colin Ross; Elizabeth M Simpson; Jan M Friedman; Clara van Karnebeek; Blair R Leavitt Journal: Hum Mol Genet Date: 2020-11-25 Impact factor: 6.150
Authors: Elizabeth E Palmer; Deborah Schofield; Rupendra Shrestha; Tejaswi Kandula; Rebecca Macintosh; John A Lawson; Ian Andrews; Hugo Sampaio; Alexandra M Johnson; Michelle A Farrar; Michael Cardamone; David Mowat; George Elakis; William Lo; Ying Zhu; Kevin Ying; Paula Morris; Jiang Tao; Kerith-Rae Dias; Michael Buckley; Marcel E Dinger; Mark J Cowley; Tony Roscioli; Edwin P Kirk; Ann Bye; Rani K Sachdev Journal: Mol Genet Genomic Med Date: 2018-01-04 Impact factor: 2.183