Mitochondrial Depletion Syndromes

  • Sumit Parikh
  • Rita Horvath


Mitochondrial DNA (mtDNA) depletion syndromes are characterized by a reduced number of mtDNA compared to nuclear DNA in affected tissues. The molecular cause of these clinically very heterogeneous diseases is autosomal recessive mutations in at least 15 nuclear genes involved in nuclear-mitochondrial inter-genomic signaling pathways. The phenotypes for these disorders can be quite varied from isolated ophthalmoplegia to multi-system disease. Almost all of the mtDNA depletion disorders can present with isolated chronic progressive ophthalmoplegia (CPEO). More extensive involvement leads to one of several various phenotypes with a primary myopathic, cardiomyopathic, encephalomyopathic, hepatocerebral, or neurogastrointestinal presentation. These categorizations, while imperfect, provide some structure around which to organize the diverse presentations of mtDNA depletion diseases. Most of these disorders have additional less common presentations, and these phenotypes are discussed within the context of the above categories.

In this chapter we discuss the clinical presentations and the latest updates in the state-of-the-art diagnosis and treatment of mtDNA maintenance diseases, including the compilation of new genes, new findings on why and how these dysfunctional genes and related proteins lead to the associated severe symptoms, as well as preclinical and clinical evidence on the plausibility of new treatments.


Mitochondrial DNA depletion disorders 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sumit Parikh
    • 1
  • Rita Horvath
    • 2
  1. 1.Mitochondrial Medicine Center, Neurological InstituteCleveland ClinicClevelandUSA
  2. 2.Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic MedicineNewcastle UniversityNewcastle Upon TyneUK

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