title: Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II.
abstract: OBJECTIVE
  To describe the clinical and biological findings of two Japanese siblings with novel MPV17 gene mutations (c.451insC/c.509C > T) manifesting hepatic mitochondrial DNA depletion syndrome.
  
  
  METHODS
  We observed these brothers and sought to determine the efficacy of treatment targeting respiratory chain complex II for the younger brother.
  
  
  RESULTS
  A 3-month-old boy had presented with profound liver dysfunction, failure to thrive, and watery diarrhea. Although he was then placed on a carbohydrate-rich diet, his liver function thereafter fluctuated greatly in association with viral infections, and rapidly deteriorated to liver failure. He underwent liver transplantation at 17 months of age but died at 22 months of age. The younger brother, aged 47 months at the time of this writing, presented with liver dysfunction from 8 months of age. His transaminase levels also fluctuated considerably fluctuations in association with viral infections. At 31 months of age, treatment with succinate and ubiquinone was initiated together with a lipid-rich diet using ketone milk. Thereafter, his transaminase levels normalized and never fluctuated, and the liver histology improved.
  
  
  CONCLUSIONS
  These cases suggested that the clinical courses of patients with MPV17 mutations are greatly influenced by viral infections and that dietary and pharmaceutical treatments targeting the mitochondrial respiratory chain complex II may be beneficial in the clinical management of MPV17 mutant patients.
authors.affiliation: Department of Pediatrics, Tsuyama Central Hospital, Tsuyama-shi, Okayama 708-0841, Japan. skaji@tvt.ne.jp
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Kaji
authors.forename: Kei
authors.initials: K
authors.lastname: Murayama
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nagata
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagasaka
authors.forename: Masaki
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtake
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iwasa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Harashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Eitoku
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsushita
authors.forename: Koichi
authors.initials: K
authors.lastname: Kitamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katayama
authors.forename: Shuji
authors.initials: S
authors.lastname: Sugimoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Jun
authors.initials: J
authors.lastname: Murakami
authors.forename: Susumu
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D002331:Carnitine / Q000627:therapeutic use; D002675:Child, Preschool; D042963:Electron Transport Complex II / Q000187:drug effects*; D017809:Fatal Outcome; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000150:complications / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000187:drug effects* / Q000235:genetics; D019802:Succinic Acid / Q000627:therapeutic use; D014451:Ubiquinone / Q000627:therapeutic use
chemical_list: C530370:MPV17 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C478189:respiratory complex II; D014451:Ubiquinone; D019802:Succinic Acid; D042963:Electron Transport Complex II; D002331:Carnitine