title: Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report.
abstract: BACKGROUND
  Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn error of metabolism inherited in autosomal recessive pattern and is associated with a wide spectrum of neurological abnormalities.
  
  
  METHODS
  We herein describe a 15-year-old boy with MTHFR deficiency who presented with a slowly progressive decline of school performance and a spastic gait. Rapidly deteriorating psychosis and repetitive seizures triggered by a febrile infection prompted neurological investigation. He had significantly elevated total plasma homocysteine and urinary homocystine levels, as well as a decreased plasma methionine level. Brain magnetic resonance imaging (MRI) revealed leukoencephalopathy. DNA gene sequencing showed c.446_447 del GC ins TT and c.137G > A, and c.665C > T heterozygous mutations in the MTHFR gene of the patient. Oral administration of betaine drastically improved his clinical symptoms within a few months. After 8 months of treatment, his total plasma homocysteine level moderately decreased; and the plasma methionine concentration became normalized. Furthermore, the white matter lesions on MRI had disappeared.
  
  
  CONCLUSIONS
  This patient demonstrates the possibility that MTHFR deficiency should be considered in mentally retarded adolescents who display an abnormally elevated plasma level of homocysteine in association with progressive neurological dysfunction and leukoencephalopathy. Febrile infections may be an aggravating factor in patients with MTHFR deficiency.
authors.affiliation: Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Iida
authors.affiliation: Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan. nakamuma@hirakata.kmu.ac.jp.
authors.forename: Masataka
authors.identifier: http://orcid.org/0000-0002-0439-5682
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Asayama
authors.affiliation: Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan.
authors.forename: Takenobu
authors.initials: T
authors.lastname: Kunieda
authors.affiliation: Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Department of Pediatrics, Jichi Medical School, 3311-1, Yakushiji, Shimotsuke-shi, Tochigi, 3290498, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
authors.affiliation: Department of Neurology, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 5731010, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kusaka
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D006712:Homocystinuria / Q000503:physiopathology*; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000097:blood; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency* / Q000235:genetics; D009128:Muscle Spasticity / Q000209:etiology / Q000503:physiopathology*; D009154:Mutation; D011618:Psychotic Disorders / Q000209:etiology* / Q000503:physiopathology
chemical_list: D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Betaine; Leukoencephalopathy; MTHFR; Psychosis; Spastic paraplegia