title: Fever of unknown origin as the initial manifestation of valproate-induced Fanconi syndrome.
abstract: BACKGROUND
  Valproate-induced Fanconi syndrome is a rare adverse effect of valproate. Severely disabled patients who require tube feeding are reported to be susceptible to valproate-induced Fanconi syndrome. Although most patients with valproate-induced Fanconi syndrome are asymptomatic and detected incidentally with findings such as hypophosphatemia, hypouricemia, increased urinary β2-microglobulin, and generalized hyperaminoaciduria, clinical symptoms such as bone fracture, fever, tachypnea, and edema have been reported.
  
  
  METHODS
  This 15-year-old, severely disabled, tube-fed, male patient with cytochrome oxidase deficiency had taken valproate for 3 years when he developed fever for 3 weeks. Hypophosphatemia, hypouricemia, hypokalemia, increased urinary β2-microglobulin, and generalized hyperaminoaciduria, as well as hypocarnitinemia, were found, indicating that he had Fanconi syndrome. Valproate was the most likely cause of Fanconi syndrome in this patient. After discontinuation of valproate, the fever resolved immediately, and the laboratory findings normalized.
  
  
  CONCLUSIONS
  Valproate-induced Fanconi syndrome should be considered when individuals taking valproate develop fever of unknown origin.
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Moriyama-shi, Shiga, Japan. Electronic address: nozaki-kgw@umin.ac.jp.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Nozaki
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Moriyama-shi, Shiga, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Moriyama-shi, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kusunoki
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, Moriyama-shi, Shiga, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Metabolism, Chiba Children's Hospital, Midori, Chiba, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Murayama
authors.affiliation: Faculty of Medicine, Department of Pediatrics, Saitama Medical University, Saitama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtake
mesh_terms: D000293:Adolescent; D030401:Cytochrome-c Oxidase Deficiency / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005198:Fanconi Syndrome / Q000139:chemically induced* / Q000150:complications / Q000503:physiopathology*; D005335:Fever of Unknown Origin / Q000503:physiopathology*; D006801:Humans; D008297:Male; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid
keywords: Fanconi syndrome; fever of unknown origin; side effects; valproate; valproate-induced Fanconi syndrome