Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment

Detalhes bibliográficos
Autor(a) principal: Temudo, T
Data de Publicação: 2009
Outros Autores: Rios, M, Prior, C, Carrilho, I, Santos, M, Maciel, P, Sequeiros, J, Fonseca, M, Monteiro, J, Cabral, P, Vieira, JP, Ormazabal, A, Artuch, R
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.17/2336
Resumo: Background: Rett disorder (RD) is a progressive neurodevelopmental entity caused by mutations in the MECP2 gene. It has been postulated that there are alterations in the levels of certain neurotransmitters and folate in the pathogenesis of this disease. Here we re-evaluated this hypothesis. Patients and Methods: We evaluated CSF folate, biogenic amines and pterines in 25 RD patients. Treatment with oral folinic acid was started in those cases with low folate. Patients were clinically evaluated and videotaped up to 6 months after therapy. Results: CSF folate was below the reference values in 32% of the patients. Six months after treatment no clinical improvement was observed. Three of the four patients with the R294X mutation had increased levels of a dopamine metabolite associated to a particular phenotype. Three patients had low levels of a serotonin metabolite. Two of them were treated with fluoxetine and one showed clinical improvement. No association was observed between CSF folate and these metabolites, after adjusting for the patients age and neopterin levels. Conclusion: Our results support that folinic acid supplementation has no significant effects on the course of the disease. We report discrete and novel neurotransmitter abnormalities that may contribute to the pathogenesis of RD highlighting the need for further studies on CSF neurotransmitters in clinically and genetically well characterized patients.
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spelling Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of TreatmentFolic Acid/cerebrospinal fluidLeucovorin/therapeutic useNeurotransmitter Agents/cerebrospinal fluidRett Syndrome/cerebrospinal fluidRett Syndrome/drug therapyAdministration, OralFolic Acid/analogs & derivativesFluoxetine/therapeutic useFluoxetine/administration & dosageHomovanillic Acid/cerebrospinal fluidHydroxyindoleacetic Acid/cerebrospinal fluidLeucovorin/administration & dosageMethyl-CpG-Binding Protein 2/geneticsPolymerase Chain ReactionRett Syndrome/geneticsSeizures/drug therapySerotonin Uptake Inhibitors/administration & dosageStereotyped Behavior/drug effectsTreatment OutcomeVitamin B Complex/therapeutic useChildHDE NEU PEDBackground: Rett disorder (RD) is a progressive neurodevelopmental entity caused by mutations in the MECP2 gene. It has been postulated that there are alterations in the levels of certain neurotransmitters and folate in the pathogenesis of this disease. Here we re-evaluated this hypothesis. Patients and Methods: We evaluated CSF folate, biogenic amines and pterines in 25 RD patients. Treatment with oral folinic acid was started in those cases with low folate. Patients were clinically evaluated and videotaped up to 6 months after therapy. Results: CSF folate was below the reference values in 32% of the patients. Six months after treatment no clinical improvement was observed. Three of the four patients with the R294X mutation had increased levels of a dopamine metabolite associated to a particular phenotype. Three patients had low levels of a serotonin metabolite. Two of them were treated with fluoxetine and one showed clinical improvement. No association was observed between CSF folate and these metabolites, after adjusting for the patients age and neopterin levels. Conclusion: Our results support that folinic acid supplementation has no significant effects on the course of the disease. We report discrete and novel neurotransmitter abnormalities that may contribute to the pathogenesis of RD highlighting the need for further studies on CSF neurotransmitters in clinically and genetically well characterized patients.ElsevierRepositório do Centro Hospitalar Universitário de Lisboa Central, EPETemudo, TRios, MPrior, CCarrilho, ISantos, MMaciel, PSequeiros, JFonseca, MMonteiro, JCabral, PVieira, JPOrmazabal, AArtuch, R2015-11-11T11:58:18Z20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/2336engBrain Develop. 2009 Jan; 31 (1): 46-51info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T09:36:28Zoai:repositorio.chlc.min-saude.pt:10400.17/2336Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:19:41.867276Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
title Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
spellingShingle Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
Temudo, T
Folic Acid/cerebrospinal fluid
Leucovorin/therapeutic use
Neurotransmitter Agents/cerebrospinal fluid
Rett Syndrome/cerebrospinal fluid
Rett Syndrome/drug therapy
Administration, Oral
Folic Acid/analogs & derivatives
Fluoxetine/therapeutic use
Fluoxetine/administration & dosage
Homovanillic Acid/cerebrospinal fluid
Hydroxyindoleacetic Acid/cerebrospinal fluid
Leucovorin/administration & dosage
Methyl-CpG-Binding Protein 2/genetics
Polymerase Chain Reaction
Rett Syndrome/genetics
Seizures/drug therapy
Serotonin Uptake Inhibitors/administration & dosage
Stereotyped Behavior/drug effects
Treatment Outcome
Vitamin B Complex/therapeutic use
Child
HDE NEU PED
title_short Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
title_full Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
title_fullStr Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
title_full_unstemmed Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
title_sort Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
author Temudo, T
author_facet Temudo, T
Rios, M
Prior, C
Carrilho, I
Santos, M
Maciel, P
Sequeiros, J
Fonseca, M
Monteiro, J
Cabral, P
Vieira, JP
Ormazabal, A
Artuch, R
author_role author
author2 Rios, M
Prior, C
Carrilho, I
Santos, M
Maciel, P
Sequeiros, J
Fonseca, M
Monteiro, J
Cabral, P
Vieira, JP
Ormazabal, A
Artuch, R
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE
dc.contributor.author.fl_str_mv Temudo, T
Rios, M
Prior, C
Carrilho, I
Santos, M
Maciel, P
Sequeiros, J
Fonseca, M
Monteiro, J
Cabral, P
Vieira, JP
Ormazabal, A
Artuch, R
dc.subject.por.fl_str_mv Folic Acid/cerebrospinal fluid
Leucovorin/therapeutic use
Neurotransmitter Agents/cerebrospinal fluid
Rett Syndrome/cerebrospinal fluid
Rett Syndrome/drug therapy
Administration, Oral
Folic Acid/analogs & derivatives
Fluoxetine/therapeutic use
Fluoxetine/administration & dosage
Homovanillic Acid/cerebrospinal fluid
Hydroxyindoleacetic Acid/cerebrospinal fluid
Leucovorin/administration & dosage
Methyl-CpG-Binding Protein 2/genetics
Polymerase Chain Reaction
Rett Syndrome/genetics
Seizures/drug therapy
Serotonin Uptake Inhibitors/administration & dosage
Stereotyped Behavior/drug effects
Treatment Outcome
Vitamin B Complex/therapeutic use
Child
HDE NEU PED
topic Folic Acid/cerebrospinal fluid
Leucovorin/therapeutic use
Neurotransmitter Agents/cerebrospinal fluid
Rett Syndrome/cerebrospinal fluid
Rett Syndrome/drug therapy
Administration, Oral
Folic Acid/analogs & derivatives
Fluoxetine/therapeutic use
Fluoxetine/administration & dosage
Homovanillic Acid/cerebrospinal fluid
Hydroxyindoleacetic Acid/cerebrospinal fluid
Leucovorin/administration & dosage
Methyl-CpG-Binding Protein 2/genetics
Polymerase Chain Reaction
Rett Syndrome/genetics
Seizures/drug therapy
Serotonin Uptake Inhibitors/administration & dosage
Stereotyped Behavior/drug effects
Treatment Outcome
Vitamin B Complex/therapeutic use
Child
HDE NEU PED
description Background: Rett disorder (RD) is a progressive neurodevelopmental entity caused by mutations in the MECP2 gene. It has been postulated that there are alterations in the levels of certain neurotransmitters and folate in the pathogenesis of this disease. Here we re-evaluated this hypothesis. Patients and Methods: We evaluated CSF folate, biogenic amines and pterines in 25 RD patients. Treatment with oral folinic acid was started in those cases with low folate. Patients were clinically evaluated and videotaped up to 6 months after therapy. Results: CSF folate was below the reference values in 32% of the patients. Six months after treatment no clinical improvement was observed. Three of the four patients with the R294X mutation had increased levels of a dopamine metabolite associated to a particular phenotype. Three patients had low levels of a serotonin metabolite. Two of them were treated with fluoxetine and one showed clinical improvement. No association was observed between CSF folate and these metabolites, after adjusting for the patients age and neopterin levels. Conclusion: Our results support that folinic acid supplementation has no significant effects on the course of the disease. We report discrete and novel neurotransmitter abnormalities that may contribute to the pathogenesis of RD highlighting the need for further studies on CSF neurotransmitters in clinically and genetically well characterized patients.
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-01-01T00:00:00Z
2015-11-11T11:58:18Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.17/2336
url http://hdl.handle.net/10400.17/2336
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Brain Develop. 2009 Jan; 31 (1): 46-51
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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