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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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 |
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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 |
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