Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II.
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.
Kaji
Shunsaku
S
Department of Pediatrics, Tsuyama Central Hospital, Tsuyama-shi, Okayama 708-0841, Japan. skaji@tvt.ne.jp
Murayama
Kei
K
Nagata
Ikuo
I
Nagasaka
Hironori
H
Takayanagi
Masaki
M
Ohtake
Akira
A
Iwasa
Hiroyasu
H
Nishiyama
Masahiko
M
Okazaki
Yasushi
Y
Harashima
Hiroko
H
Eitoku
Takahiro
T
Yamamoto
Michiko
M
Matsushita
Hiroaki
H
Kitamoto
Koichi
K
Sakata
Shinji
S
Katayama
Takeshi
T
Sugimoto
Shuji
S
Fujimoto
Yoshio
Y
Murakami
Jun
J
Kanzaki
Susumu
S
Shiraki
Kazuo
K
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
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