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

• Published in: Brain & development (Tokyo. 1979) Vol. 31; no. 1; pp. 46 - 51
• Main Authors: Temudo, T, Rios, M, Prior, C, Carrilho, I, Santos, M, Maciel, P, Sequeiros, J, Fonseca, M, Monteiro, J, Cabral, P, Vieira, J.P, Ormazabal, A, Artuch, R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2009; Elsevier
• Subjects: Administration; Administration, Oral; Child; Child, Preschool; DNA Mutational Analysis; DNA Mutational Analysis - methods; Female; Fluoxetine; Fluoxetine - administration & dosage; Fluoxetine - therapeutic use; Folate; Folic Acid; Folic Acid - analogs & derivatives; Folic Acid - cerebrospinal fluid; Homovanillic Acid; Homovanillic Acid - cerebrospinal fluid; Humans; Hydroxyindoleacetic Acid; Hydroxyindoleacetic Acid - cerebrospinal fluid; Leucovorin; Leucovorin - administration & dosage; Leucovorin - therapeutic use; Methyl-CpG-Binding Protein 2 - genetics; Movement disorders; Mutation; Neurology; Neurotransmitter Agents; Neurotransmitter Agents - cerebrospinal fluid; Neurotransmitters; Oral; Polymerase Chain Reaction; Preschool; Rett Syndrome; Rett Syndrome - cerebrospinal fluid; Rett Syndrome - drug therapy; Rett Syndrome - genetics; Science & Technology; Seizures; Seizures - drug therapy; Serotonin Uptake Inhibitors; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - therapeutic use; Stereotyped Behavior; Stereotyped Behavior - drug effects; Treatment Outcome; Vitamin B Complex; Vitamin B Complex - administration & dosage; Vitamin B Complex - therapeutic use; Neurotransmitters; Folate; Movement disorders; Rett syndrome
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/j.braindev.2008.05.003

Abstract 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.