title: Pyridoxine-dependent epilepsy: report on three families with neuropathology.
abstract: 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.
authors.affiliation: Pathology Laboratory, Rouen University Hospital, Rouen, France.|Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Marguet
authors.affiliation: Department of Pediatrics, Military Hospital of Tunis, Tunis, Tunisia.
authors.forename: Hager
authors.initials: H
authors.lastname: Barakizou
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France.|Department of Metabolic Biochemistry, Rouen University Hospital, 1 Rue de Germont, 76031, Rouen Cedex, France.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Tebani
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France.|Department of Neonatology, Intensive care unit, and Neuropediatrics, Rouen University Hospital, Rouen, France.
authors.forename: Lenaig
authors.initials: L
authors.lastname: Abily-Donval
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France.|Department of Neonatology, Intensive care unit, and Neuropediatrics, Rouen University Hospital, Rouen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Torre
authors.affiliation: Department of Pediatrics, Military Hospital of Tunis, Tunis, Tunisia.
authors.forename: Fethi
authors.initials: F
authors.lastname: Bayoudh
authors.affiliation: Department of Pediatrics, Clinique Avicenne Tunis, Tunis, Tunisia.
authors.forename: Sami
authors.initials: S
authors.lastname: Jebnoun
authors.affiliation: Department of Radiology, Rouen University Hospital, Rouen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Brasseur-Daudruy
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France.|Department of Neonatology, Intensive care unit, and Neuropediatrics, Rouen University Hospital, Rouen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.affiliation: Pathology Laboratory, Rouen University Hospital, Rouen, France.|Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerriere
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, CHU Rouen, IRIB, Laboratoire NeoVasc ERI28, Rouen, 76000, France. soumeya.bekri@chu-rouen.fr.|Department of Metabolic Biochemistry, Rouen University Hospital, 1 Rue de Germont, 76031, Rouen Cedex, France. soumeya.bekri@chu-rouen.fr.
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
mesh_terms: D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D004827:Epilepsy / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011736:Pyridoxine / Q000008:administration & dosage
chemical_list: D011736:Pyridoxine
keywords: Antiquitin; Long-term outcome; Molecular analyses; Neuropathology; Pyridoxine-dependent epilepsy