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Clinical and biochemical outcome of a patient with pyridoxine-dependent epilepsy treated by triple therapy (pyridoxine supplementation, lysine-restricted diet, and arginine supplementation)

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Abstract

Pyridoxine-dependent epilepsy (PDE) is a recessive genetic disease characterized by epileptic encephalopathy with therapeutic response to pharmacological doses of pyridoxine and resistance to anti-epileptic treatments. The recent discovery in 2006 of the genetic defect antiquitin (ALDH7A1, OMIM #266100) has helped to understand the underlying mechanism, which is the accumulation of neurotoxic intermediates in the lysine catabolic pathway. The goal of the new therapeutic approach, termed triple therapy (TT) (pyridoxine, lysine-restricted diet and arginine supplementation), is to improve epilepsy control and neurocognitive development in patients with PDE. We present the 3-year treatment outcome for a child with PDE on pyridoxine treatment (started at age 5 months), lysine-restricted diet (started at age 17 months) and arginine supplementation therapy (started at age 19 months). The TT was well-tolerated with good compliance. No adverse events were reported. We observed a neurodevelopmental improvement, significantly fewer seizures, and a reduction of pipecolic acid (PA) as a biomarker of the illness. Our results show an improving clinical evolution, supporting and extending previous studies reporting efficacy of TT.

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Authors and Affiliations

  1. Service de Néonatologie, Hôpital Estaing, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France

    Perrine Minet & Ganaelle Remerand

  2. Service de Génétique Médicale, Hôpital Estaing, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France

    Catherine Sarret & Ania Miret

  3. Centre de Référence Des Maladies Héréditaires du Métabolisme, Pôle Enfant, Centre Hospitalier Universitaire de Lille-Hôpital Jeanne de Flandre, Lille, France

    Karine Mention

  4. Service de Biochimie-Hormonologie, Centre Hospitalier Universitaire de Paris-Hôpital Robert Debré, Paris, France

    Jean François Benoist

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  1. Perrine Minet
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  2. Catherine Sarret
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Correspondence to Ganaelle Remerand.

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C Sarret has been a member of a scientific board for Biogen Laboratories. The other authors declare they have no conflict of interest.

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Minet, P., Sarret, C., Miret, A. et al. Clinical and biochemical outcome of a patient with pyridoxine-dependent epilepsy treated by triple therapy (pyridoxine supplementation, lysine-restricted diet, and arginine supplementation). Acta Neurol Belg 121, 1669–1675 (2021). https://doi.org/10.1007/s13760-020-01467-3

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  • DOI: https://doi.org/10.1007/s13760-020-01467-3

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