Document Detail


Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II.
MedLine Citation:
PMID:  19520594     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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; Kazuo Shiraki
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-12
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  97     ISSN:  1096-7206     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-13     Completed Date:  2009-09-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  292-6     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Tsuyama Central Hospital, Tsuyama-shi, Okayama 708-0841, Japan. skaji@tvt.ne.jp
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MeSH Terms
Descriptor/Qualifier:
Carnitine / therapeutic use
Child, Preschool
Electron Transport Complex II / drug effects*
Fatal Outcome
Humans
Infant
Liver / metabolism*
Liver Diseases / complications,  diet therapy,  drug therapy,  metabolism*,  virology
Liver Transplantation
Male
Membrane Proteins / drug effects*,  genetics
Mitochondrial Proteins / drug effects*,  genetics
Succinic Acid / therapeutic use
Ubiquinone / therapeutic use
Chemical
Reg. No./Substance:
0/MPV17 protein, human; 0/Membrane Proteins; 0/Mitochondrial Proteins; 110-15-6/Succinic Acid; 1339-63-5/Ubiquinone; 541-15-1/Carnitine; EC 1.3.5.1/Electron Transport Complex II; EC 1.6.5.3/respiratory complex II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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