Pyridoxine-dependent epilepsy: report on three families with neuropathology

Autor: Florent Marguet, Annie Laquerrière, Abdellah Tebani, Stéphane Marret, Lenaig Abily-Donval, M. Brasseur-Daudruy, Fethi Bayoudh, Stéphanie Torre, Hager Barakizou, Sami Jebnoun, Soumeya Bekri
Přispěvatelé: Department of Pathology, Rouen University Hospital, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Team 4 'NeoVasc' - INSERM U1245, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital militaire-Tunis, Service d'imagerie médicale [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Metabolic Brain Disease
Metabolic Brain Disease, Springer Verlag, 2016, 31 (6), pp.1435-1443. ⟨10.1007/s11011-016-9869-z⟩
ISSN: 0885-7490
1573-7365
Popis: Pyridoxine-dependent epilepsy (PDE) is a pharmacoresistant epileptogenic encephalopathy controlled by pyridoxine supplementation at pharmacological doses. Despite supplementation, the long-term outcome is often poor possibly because of recurrent seizures and developmental structural brain abnormalities. We report on five patients with PDE from three unrelated families. The diagnosis was confirmed by ALDH7A1 sequencing, which allowed for the characterization of two homozygous variations [NM_001182.3:c.1279G > C - p.(Glu427Gln) and c.834G > A - p.(Val278Val)]. Brain autopsy was conducted for one untreated patient with molecularly confirmed antiquitin deficiency. Macroscopic and histological examination revealed a combination of lesions resulting from recurrent seizures and consisting of extensive areas of cortical necrosis, gliosis, and hippocampic sclerosis. The examination also revealed developmental abnormalities including corpus callosum dysgenesis and corticospinal pathfinding anomalies. This case is the second to be reported in the literature, and our findings show evidence that antiquitin is required for normal brain development and functioning. Despite prophylactic prenatal pyridoxine supplementation during the last trimester of pregnancy in one of the three families and sustained pyridoxine treatment in three living patients, the clinical outcome remained poor with delayed acquisition of neurocognitive skills. Combined therapy (pyridoxine/arginine supplementation and lysine-restricted diet) should be considered early in the course of the disease for a better long-term outcome. Enhanced knowledge of PDE features is required to improve treatment strategies.
Databáze: OpenAIRE
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