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Genetic Basis of Mitochondrial Cardiomyopathy

  • Elisa Mastantuono
  • Cordula Maria Wolf
  • Holger ProkischEmail author
Chapter
Part of the Cardiac and Vascular Biology book series (Abbreviated title: Card. vasc. biol., volume 7)

Abstract

Mitochondrial disorders are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial energy metabolism, and they represent one of the largest groups of inborn errors of metabolism. Mitochondrial disorders can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA (mtDNA), with more than 300 disease-associated genes identified to date. Among these genes, around 100 have so far been associated with cardiac manifestations. Cardiomyopathy is estimated to occur in 20–40% of children with mitochondrial disorders. Genetic defects can affect a vast range of different mitochondrial functions including electron transport chain complex subunits and their assembly factors, mitochondrial transfer or ribosomal RNAs, factors involved in translation or mtDNA maintenance, and cofactor metabolism such as coenzyme Q10 synthesis. With collectively more than 1000 described cases, the most frequent mitochondrial cardiac diseases include Barth syndrome, Sengers syndrome, ACAD9- or TMEM70-related mitochondrial complex I or V deficiency, and Friedreich ataxia. Hypertrophic cardiomyopathy is the most common type of cardiomyopathy, but mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular non-compaction, and histiocytoid cardiomyopathies. Mitochondrial cardiomyopathy can vary in severity from asymptomatic to severe manifestations including heart failure and sudden cardiac death. Congenital arrhythmias and congenital heart defects (CHDs) are also part of the clinical spectrum of mitochondrial disorders. In this chapter, we provide an overview of the constantly growing number of mitochondrial cardiac disorders and comment on the current practice in the diagnosis and treatment of patients with mitochondrial cardiomyopathy, including optimal therapeutic management and long-term monitoring.

Keywords

Mitochondrial disorders Cardiomyopathy Genetic defects Whole-exome sequencing 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Elisa Mastantuono
    • 1
    • 2
    • 3
  • Cordula Maria Wolf
    • 4
  • Holger Prokisch
    • 1
    • 2
    Email author
  1. 1.Institute of Human Genetics, Technische Universität MünchenMunichGermany
  2. 2.Institute of Human Genetics, Helmholtz Zentrum MünchenMunichGermany
  3. 3.DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart AllianceMunichGermany
  4. 4.Department of Pediatric Cardiology and Congenital Heart Defects, German Heart Center MunichTechnical University MunichMunichGermany

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