title: Determination of CSF 5-methyltetrahydrofolate in children and its application for defects of folate transport and metabolism.
abstract: OBJECTIVE
  To describe an assay of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF) of children, to determine reference values, and to report the clinical significance of this assay in metabolic disorders affecting folate transport and metabolism.
  
  
  METHODS
  CSF 5MTHF was determined by high-performance liquid chromatography with fluorescent detection in pediatric patients including one with FOLR1 gene mutation and one with methylenetetrahydrofolate reductase (MTHFR) deficiency. CSF total folate was measured using an automated analyzer.
  
  
  RESULTS
  5MTHF and total folate were determined in 188 and 93 CSF samples, respectively. CSF 5MTHF was high throughout the first six months of life and subsequently declined with age. Reference values of CSF 5MTHF and total folate were determined from 162 and 82 samples, respectively. The patient with FOLR1 gene mutation had extremely low CSF 5MTHF and total folate, though these values normalized after folinic acid supplementation. The patient with MTHFR deficiency had extremely low 5MTHF and moderately low total folate; these values were not associated and showed no significant change after folic acid supplementation.
  
  
  CONCLUSIONS
  This 5MTHF assay is simple, rapid, sensitive, reliable, and cost-effective. It will aid in the diagnosis and therapeutic monitoring of metabolic disorders affecting folate transport and metabolism.
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Akiyama
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Japan. Electronic address: takiyama@okayama-u.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Faculty of Medicine, Okayama University, Okayama, Japan.
authors.forename: Kaoruko
authors.initials: K
authors.lastname: Kanamaru
authors.affiliation: Faculty of Medicine, Okayama University, Okayama, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Kuribayashi
authors.affiliation: Division of Instrumental Analysis, Department of Instrumental Analysis and Cryogenics, Advanced Science Research Center, Okayama University, Okayama, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tada
authors.affiliation: Division of Instrumental Analysis, Department of Instrumental Analysis and Cryogenics, Advanced Science Research Center, Okayama University, Okayama, Japan.
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Shiokawa
authors.affiliation: Department of Pediatrics, Kameda Medical Center, Chiba, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Toda
authors.affiliation: Department of Pediatrics, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Child Neurology, NHO Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Child Neurology, NHO Nishi-Niigata Chuo National Hospital, Niigata, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Tohyama
authors.affiliation: Department of Pediatrics, Nara Medical University, Nara, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sakakibara
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Japan; Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Yoshinaga
authors.affiliation: Department of Child Neurology, Okayama University Hospital, Okayama, Japan; Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D019963:Clinical Chemistry Tests / Q000379:methods; D019587:Dietary Supplements; D058975:Folate Receptor 1 / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D006712:Homocystinuria; D006801:Humans; D007223:Infant; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency; D009128:Muscle Spasticity; D011618:Psychotic Disorders; D012016:Reference Values; D013763:Tetrahydrofolates / Q000134:cerebrospinal fluid*
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D013763:Tetrahydrofolates; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C005984:5-methyltetrahydrofolate
keywords: FOLR1 gene mutation; High-performance liquid chromatography; MTHFR deficiency; Reference value