Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment.
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.


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.


CONCLUSIONS
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.
Unidade de Neuropediatria, Serviço de Pediatria, Hospital Geral de Santo António, SA, Largo Abel Salazar, 4099/001 Porto, Portugal. teresatemudo@netcabo.pt
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Temudo
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Rios
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Prior
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Carrilho
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Santos
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Maciel
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Sequeiros
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Fonseca
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Monteiro
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Cabral
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Vieira
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Ormazabal
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Artuch
D000284:Administration, Oral; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use; D005492:Folic Acid / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D016133:Polymerase Chain Reaction; D015518:Rett Syndrome / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000235:genetics; D012640:Seizures / Q000188:drug therapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013239:Stereotyped Behavior / Q000187:drug effects; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use
D005473:Fluoxetine; D005492:Folic Acid; D006719:Homovanillic Acid; D006897:Hydroxyindoleacetic Acid; D002955:Leucovorin; D051783:Methyl-CpG-Binding Protein 2; D018377:Neurotransmitter Agents; D017367:Selective Serotonin Reuptake Inhibitors; D014803:Vitamin B Complex; C032418:5,11-methenyltetrahydrohomofolate