Cargando…

Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease

Cerebral folate deficiency (CFD) is a neurological disorder characterized by low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF). The prevalence of this autosomal recessive disorder is estimated to be <1/1,000,000. Fifteen different pathogenic variants in the folate r...

Descripción completa

Detalles Bibliográficos
Autores principales: Mafi, Sarah, Laroche-Raynaud, Cécile, Chazelas, Pauline, Lia, Anne-Sophie, Derouault, Paco, Sturtz, Franck, Baaj, Yasser, Froget, Rachel, Rio, Marlène, Benoist, Jean-François, Poumeaud, François, Favreau, Frédéric, Faye, Pierre-Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690394/
https://www.ncbi.nlm.nih.gov/pubmed/33105619
http://dx.doi.org/10.3390/brainsci10110762
_version_ 1783614057884942336
author Mafi, Sarah
Laroche-Raynaud, Cécile
Chazelas, Pauline
Lia, Anne-Sophie
Derouault, Paco
Sturtz, Franck
Baaj, Yasser
Froget, Rachel
Rio, Marlène
Benoist, Jean-François
Poumeaud, François
Favreau, Frédéric
Faye, Pierre-Antoine
author_facet Mafi, Sarah
Laroche-Raynaud, Cécile
Chazelas, Pauline
Lia, Anne-Sophie
Derouault, Paco
Sturtz, Franck
Baaj, Yasser
Froget, Rachel
Rio, Marlène
Benoist, Jean-François
Poumeaud, François
Favreau, Frédéric
Faye, Pierre-Antoine
author_sort Mafi, Sarah
collection PubMed
description Cerebral folate deficiency (CFD) is a neurological disorder characterized by low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF). The prevalence of this autosomal recessive disorder is estimated to be <1/1,000,000. Fifteen different pathogenic variants in the folate receptor 1 gene (FOLR1) encoding the receptor of folate α (FRα) have already been described. We present a new pathogenic variation in the FOLR1 in a childhood-stage patient. We aim to establish the core structure of the FRα protein mandatory for its activity. A three-year-old child was admitted at hospital for a first febrile convulsions episode. Recurrent seizures without fever also occurred a few months later, associated with motor and cognitive impairment. Various antiepileptic drugs failed to control seizures. Magnetic resonance imaging (MRI) showed central hypomyelination and biological analysis revealed markedly low levels of 5-MTHF in CSF. Next generation sequencing (NGS) confirmed a CFD with a FOLR1 homozygous variation (c.197 G > A, p.Cys66Tyr). This variation induces an altered folate receptor α protein and underlines the role of a disulfide bond: Cys66-Cys109, essential to transport 5-MTHF into the central nervous system. Fortunately, this severe form of CFD had remarkably responded to high doses of oral folinic acid combined with intravenous administrations.
format Online
Article
Text
id pubmed-7690394
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76903942020-11-27 Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease Mafi, Sarah Laroche-Raynaud, Cécile Chazelas, Pauline Lia, Anne-Sophie Derouault, Paco Sturtz, Franck Baaj, Yasser Froget, Rachel Rio, Marlène Benoist, Jean-François Poumeaud, François Favreau, Frédéric Faye, Pierre-Antoine Brain Sci Case Report Cerebral folate deficiency (CFD) is a neurological disorder characterized by low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF). The prevalence of this autosomal recessive disorder is estimated to be <1/1,000,000. Fifteen different pathogenic variants in the folate receptor 1 gene (FOLR1) encoding the receptor of folate α (FRα) have already been described. We present a new pathogenic variation in the FOLR1 in a childhood-stage patient. We aim to establish the core structure of the FRα protein mandatory for its activity. A three-year-old child was admitted at hospital for a first febrile convulsions episode. Recurrent seizures without fever also occurred a few months later, associated with motor and cognitive impairment. Various antiepileptic drugs failed to control seizures. Magnetic resonance imaging (MRI) showed central hypomyelination and biological analysis revealed markedly low levels of 5-MTHF in CSF. Next generation sequencing (NGS) confirmed a CFD with a FOLR1 homozygous variation (c.197 G > A, p.Cys66Tyr). This variation induces an altered folate receptor α protein and underlines the role of a disulfide bond: Cys66-Cys109, essential to transport 5-MTHF into the central nervous system. Fortunately, this severe form of CFD had remarkably responded to high doses of oral folinic acid combined with intravenous administrations. MDPI 2020-10-22 /pmc/articles/PMC7690394/ /pubmed/33105619 http://dx.doi.org/10.3390/brainsci10110762 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Mafi, Sarah
Laroche-Raynaud, Cécile
Chazelas, Pauline
Lia, Anne-Sophie
Derouault, Paco
Sturtz, Franck
Baaj, Yasser
Froget, Rachel
Rio, Marlène
Benoist, Jean-François
Poumeaud, François
Favreau, Frédéric
Faye, Pierre-Antoine
Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease
title Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease
title_full Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease
title_fullStr Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease
title_full_unstemmed Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease
title_short Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease
title_sort pharmacoresistant epilepsy in childhood: think of the cerebral folate deficiency, a treatable disease
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690394/
https://www.ncbi.nlm.nih.gov/pubmed/33105619
http://dx.doi.org/10.3390/brainsci10110762
work_keys_str_mv AT mafisarah pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT larocheraynaudcecile pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT chazelaspauline pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT liaannesophie pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT derouaultpaco pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT sturtzfranck pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT baajyasser pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT frogetrachel pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT riomarlene pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT benoistjeanfrancois pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT poumeaudfrancois pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT favreaufrederic pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease
AT fayepierreantoine pharmacoresistantepilepsyinchildhoodthinkofthecerebralfolatedeficiencyatreatabledisease