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 Kanzaki & 1 others Kazuo Shiraki

Research output: Contribution to journalArticle

29 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 2009
Externally publishedYes

Fingerprint

Electron Transport
Liver
Siblings
Virus Diseases
Mutation
Liver Failure
Transaminases
Pharmaceutical Preparations
Liver Diseases
Nutrition
Diet
Failure to Thrive
Ubiquinone
Succinic Acid
Therapeutics
Ketones
Mitochondrial DNA
Liver Transplantation
Diarrhea
Histology

Keywords

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

ASJC Scopus subject areas

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

Cite this

Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II. / Kaji, Shunsaku; Murayama, Kei; Nagata, Ikuo; Nagasaka, Hironori; Takayanagi, Masaki; Ohtake, Akira; Iwasa, Hiroyasu; Nishiyama, Masahiko; Okazaki, Yasushi; Harashima, Hiroko; Eitoku, Takahiro; Yamamoto, Michiko; Matsushita, Hiroaki; Kitamoto, Koichi; Sakata, Shinji; Katayama, Takeshi; Sugimoto, Shuji; Fujimoto, Yoshio; Murakami, Jun; Kanzaki, Susumu; Shiraki, Kazuo.

In: Molecular Genetics and Metabolism, Vol. 97, No. 4, 08.2009, p. 292-296.

Research output: Contribution to journalArticle

Kaji, S, Murayama, K, Nagata, I, Nagasaka, H, Takayanagi, M, Ohtake, A, Iwasa, H, Nishiyama, M, Okazaki, Y, Harashima, H, Eitoku, T, Yamamoto, M, Matsushita, H, Kitamoto, K, Sakata, S, Katayama, T, Sugimoto, S, Fujimoto, Y, Murakami, J, Kanzaki, S & Shiraki, K 2009, 'Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II', Molecular Genetics and Metabolism, vol. 97, no. 4, pp. 292-296. https://doi.org/10.1016/j.ymgme.2009.04.014
Kaji, Shunsaku ; Murayama, Kei ; Nagata, Ikuo ; Nagasaka, Hironori ; Takayanagi, Masaki ; Ohtake, Akira ; Iwasa, Hiroyasu ; Nishiyama, Masahiko ; Okazaki, Yasushi ; Harashima, Hiroko ; Eitoku, Takahiro ; Yamamoto, Michiko ; Matsushita, Hiroaki ; Kitamoto, Koichi ; Sakata, Shinji ; Katayama, Takeshi ; Sugimoto, Shuji ; Fujimoto, Yoshio ; Murakami, Jun ; Kanzaki, Susumu ; Shiraki, Kazuo. / Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II. In: Molecular Genetics and Metabolism. 2009 ; Vol. 97, No. 4. pp. 292-296.
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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.",
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T1 - Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II

AU - Kaji, Shunsaku

AU - Murayama, Kei

AU - Nagata, Ikuo

AU - Nagasaka, Hironori

AU - Takayanagi, Masaki

AU - Ohtake, Akira

AU - Iwasa, Hiroyasu

AU - Nishiyama, Masahiko

AU - Okazaki, Yasushi

AU - Harashima, Hiroko

AU - Eitoku, Takahiro

AU - Yamamoto, Michiko

AU - Matsushita, Hiroaki

AU - Kitamoto, Koichi

AU - Sakata, Shinji

AU - Katayama, Takeshi

AU - Sugimoto, Shuji

AU - Fujimoto, Yoshio

AU - Murakami, Jun

AU - Kanzaki, Susumu

AU - Shiraki, Kazuo

PY - 2009/8

Y1 - 2009/8

N2 - 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.

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KW - Mitochondrial DNA depletion syndrome

KW - Mitochondrial respiratory chain complex

KW - MPV17 mutations

KW - Succinate

KW - Treatment

KW - Ubiquinone

KW - Viral infection

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