title: Mitochondrial respiratory chain disorders in childhood: insights into diagnosis and management in the new era of genomic medicine.
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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Disciplines of Paediatrics and Child Health, Sydney Medical School, University of Sydney, New South Wales, Australia; Genetic Metabolic Disorders Research Unit, Kids Research Institute, Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Minal J
authors.initials: MJ
authors.lastname: Menezes
authors.affiliation: Genetic Metabolic Disorders Research Unit, Kids Research Institute, Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Riley
authors.affiliation: Disciplines of Paediatrics and Child Health, Sydney Medical School, University of Sydney, New South Wales, Australia; Genetic Metabolic Disorders Research Unit, Kids Research Institute, Children's Hospital at Westmead, Sydney, NSW, Australia; Genetic Medicine, Sydney Medical School, University of Sydney, New South Wales, Australia. Electronic address: john.christodoulou@health.nsw.gov.au.
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D000367:Age Factors; D035843:Biomedical Research / Q000639:trends; D002648:Child; D056947:Enzyme Replacement Therapy / Q000639:trends; D005081:Exercise Therapy; D015316:Genetic Therapy / Q000639:trends; D023281:Genomics / Q000639:trends*; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000639:trends
keywords: Electron transport chain; Mutation; Oxidative phosphorylation; Respiratory chain; mtDNA