Mitochondrial respiratory chain disorders in childhood: insights into diagnosis and management in the new era of genomic medicine

Biochim Biophys Acta. 2014 Apr;1840(4):1368-79. doi: 10.1016/j.bbagen.2013.12.025. Epub 2013 Dec 28.

Abstract

Background: Mitochondrial respiratory chain disorders (MRCDs) are some of the most common metabolic disorders presenting in childhood, however because of it clinical heterogeneity, diagnosis is often challenging. Being a multisystemic disorder with variable and non-specific presentations, definitive diagnosis requires a combination of investigative approaches, and is often a laborious process.

Scope of review: In this review we provide a broad overview of the clinical presentations of MRCDs in childhood, evaluating the different diagnostic approaches and treatment options, and highlighting the recent research advances in this area.

Major conclusions: Extensive research over the years has significantly increased the frequency with which accurate diagnosis is being made, including the identification of new biomarkers and next generation sequencing (NGS) technologies. NGS has provided a breakthrough in unravelling the genetic basis of MRCDs, especially considering the complexity of mitochondrial genetics with its dual genetic contributions.

General significance: With an increased understanding of the pathophysiology of this group of disorders, clinical trials are now being established using a number of different therapeutic approaches, with the hope of changing the focus of treatment from being largely supportive to potentially having a positive effect on the natural history of the disorder. This article is part of a Special Issue entitled: Special Issue: Frontiers of Mitochondria IG000218.

Keywords: Electron transport chain; Mutation; Oxidative phosphorylation; Respiratory chain; mtDNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Biomedical Research / trends
  • Child
  • Enzyme Replacement Therapy / trends
  • Exercise Therapy
  • Genetic Therapy / trends
  • Genomics / trends*
  • Humans
  • Mitochondrial Diseases / diagnosis*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / therapy*
  • Molecular Targeted Therapy / trends