Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II

Shunsaku Kaji, Kei Murayama, Ikuo Nagata, Hironori Nagasaka, Masaki Takayanagi, Akira Ohtake, Hiroyasu Iwasa, Masahiko Nishiyama, Yasushi Okazaki, Hiroko Harashima, Takahiro Eitoku, Michiko Yamamoto, Hiroaki Matsushita, Koichi Kitamoto, Shinji Sakata, Takeshi Katayama, Shuji Sugimoto, Yoshio Fujimoto, Jun Murakami, Susumu KanzakiKazuo Shiraki

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Background/aims: 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.

Original languageEnglish
Pages (from-to)292-296
Number of pages5
JournalMolecular Genetics and Metabolism
Volume97
Issue number4
DOIs
Publication statusPublished - Aug 1 2009
Externally publishedYes

Keywords

  • Ketone milk
  • Lipid-rich diet
  • Liver dysfunction
  • MPV17 mutations
  • Mitochondrial DNA depletion syndrome
  • Mitochondrial respiratory chain complex
  • Succinate
  • Treatment
  • Ubiquinone
  • Viral infection

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Fingerprint Dive into the research topics of 'Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II'. Together they form a unique fingerprint.

Cite this