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Gastrointestinal and hepatic manifestations of mitochondrial disorders

  • SSIEM Symposium 2012
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Inherited defects of oxidative phosphorylation lead to heterogeneous, often multisystem, mitochondrial diseases. This review highlights those mitochondrial syndromes with prominent gastrointestinal and hepatic symptoms, categorised according to underlying disease mechanism. Mitochondrial encephalopathies with major gastrointestinal involvement include mitochondrial neurogastrointestinal encephalopathy and ethylmalonic encephalopathy, which are each associated with highly specific clinical and metabolic profiles. Mitochondrial hepatopathies are most frequently caused by defects of mitochondrial DNA maintenance and expression. Although mitochondrial disorders are notorious for extreme clinical, biochemical and genetic heterogeneity, there are some pathognomonic clinical and metabolic clues that suggest a specific diagnosis, and these are highlighted. An approach to diagnosis of these complex disorders is presented, together with a genetic classification, including mitochondrial DNA disorders and nuclear-encoded defects of mitochondrial DNA maintenance and translation, OXPHOS complex assembly and mitochondrial membrane lipids. Finally, supportive and experimental therapeutic options for these currently incurable diseases are reviewed, including liver transplantation, allogeneic haematopoietic stem cell transplantation and gene therapy.

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Acknowledgments

SR is supported by Great Ormond Street Hospital Children’s Charity and receives research grant funding from Ataxia UK, the Child Health Research Appeal Trust, Climb, the Medical Research Council, the Muscular Dystrophy Campaign, Sparks and The Wellcome Trust. David Smithson of UCL Medical Illustration Services provided technical assistance with the artwork.

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  1. Mitochondrial Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Shamima Rahman

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Correspondence to Shamima Rahman.

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Communicated by: John Christodoulou

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Rahman, S. Gastrointestinal and hepatic manifestations of mitochondrial disorders. J Inherit Metab Dis 36, 659–673 (2013). https://doi.org/10.1007/s10545-013-9614-2

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