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.
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.
Competing interests: None declared
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Acknowledgments
We gratefully acknowledge Mrs. Claire Sowerbutt for text editing, Mrs. Ruth Giesbrecht (B.C. Children’s Hospital) for editorial assistance, and Dr. Beate Szczerbak (Nutricia Advanced Medical Nutrition) for supporting the 3rd PDE Consortium meeting (2013). CvK is supported by TIDE-BC, the 1st Collaborative Area of Innovation grant from BC Children’s Hospital Foundation, Vancouver, Canada. PM is supported by a grant from the GOSHCC Neuroscience Initiative. The content of this article has not been influenced by the funders/supporters.
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Synopsis
The first recommendation for the implementation and monitoring of the lysine-restricted diet as adjunct treatment for PDE generated as consensus statement by the international PDE Consortium.
Conflict of Interest
Clara van Karnebeek and Hans Hartmann declare that the room rental for the 4th PDE Consortium meeting in Barcelona, Spain was sponsored by Milupa/Nutricia; a company employee was in attendance but did not contribute to the content or design of the recommendations. Clara van Karnebeek, Sylvia Stockler, Sravan Jaggumantri, Birgit Assmann, Peter Baxter, Daniela Buhas, Levinus A. Bok, Barbara Cheng, Curtis R. Coughlin II, Anibh M. Das, Alette Giezen, Wahla Al-Hertani, Gloria Ho, Uta Meyer, Philippa Mills, Barbara Plecko, Eduard Struys, Keiko Ueda, Monique Albersen, Nanda Verhoeven, Sidney M. Gospe Jr., Renata C. Gallagher, Johan Van Hove, Hans Hartmann declare that they have no (other) conflict interest to declare.
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Details of Contributions of Individual Authors’ Contributions
Clara van Karnebeek and Hans Hartmann performed the literature review, led the consensus meetings, and drafted the recommendations, revising it according to the author group’s input. Sylvia Stockler, Sravan Jaggumantri, Barbara Plecko, Sidney Gospe, Renata Gallagher, and Johan van Hove provided critical input for the content and format of the recommendations at each stage, and drafted individual parts of the manuscript. Peter Baxter, Daniela Buhas, Levinus A. Bok, Barbara Cheng, Curtis R. Coughlin II, Anibh M. Das, Alette Giezen, Wahla Al-Hertani, Gloria Ho, Uta Meyer, Philippa Mills, Barbara Plecko, Eduard Struys, Keiko Ueda, Monique Albersen, Nanda Verhoeven provided input for the recommendations specific to their field (pediatric neurology, metabolic diseases, laboratory biochemical genetics, dietetics, and nutrition), both at a clinical and scientific level. All authors are active members of the PDE Consortium and reviewed/edited the manuscript.
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van Karnebeek, C.D.M. et al. (2014). Lysine-Restricted Diet as Adjunct Therapy for Pyridoxine-Dependent Epilepsy: The PDE Consortium Consensus Recommendations. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports, Volume 15. JIMD Reports, vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_296
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