Evaluation of CSF Neurotransmitters and Folate in 25 Patients with Rett Disorder and Effects of Treatment
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , , , , |
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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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 instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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