title: Folinic acid supplementation in Rett syndrome patients does not influence the course of the disease: a randomized study.
abstract: Rett syndrome is a neurodevelopmental disorder in girls, related to mutations in MECP2 gene. It has been postulated that low 5-methyltetrahydrofolate (5-MTHF) levels are present in cerebrospinal fluid. Folinic acid demonstrated clinical improvement. However, because studies have produced conflicting results, we performed a randomized, double-blind crossover, long-term, follow-up study on folinic acid. Eight Rett syndrome patients received both folinic acid and placebo, for 1 year each. Measurements included plasma folate, 5-MTHF, and clinical outcome scores like Rett Syndrome Motor Behavioral Assessment, Hand Apraxia Scale, and the parental Overall Well-Being Index. In 2 patients, low 5-MTHF levels were present. Folinic acid supplementation increased cerebrospinal fluid 5-MTHF levels, but with no objective evidence of clinical improvement. The Overall Well-Being Index showed a significant difference in favor of folinic acid, not confirmed objectively. In our double-blind randomized study, folinic acid supplementation resulted in increased 5-MTHF levels, but with no objective signs of clinical improvement.
authors.affiliation: Academic Medical Center, Department of Pediatric Neurology, Amsterdam, The Netherlands. e.e.hagebeuk@amc.uva.nl
authors.forename: Eveline E O
authors.initials: EE
authors.lastname: Hagebeuk
authors.forename: Marinus
authors.initials: M
authors.lastname: Duran
authors.forename: Johannes H T M
authors.initials: JH
authors.lastname: Koelman
authors.forename: Nicolaas G G M
authors.initials: NG
authors.lastname: Abeling
authors.forename: Arno
authors.initials: A
authors.lastname: Vyth
authors.forename: Bwee-Tien
authors.initials: BT
authors.lastname: Poll-The
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000097:blood; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D016014:Linear Models; D008137:Longitudinal Studies; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009460:Neurologic Examination; D015518:Rett Syndrome / Q000134:cerebrospinal fluid / Q000178:diet therapy* / Q000235:genetics; D013763:Tetrahydrofolates / Q000097:blood / Q000134:cerebrospinal fluid; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D013763:Tetrahydrofolates; D005492:Folic Acid; D002955:Leucovorin; C005984:5-methyltetrahydrofolate