Minal J Menezes1, Lisa G Riley2, John Christodoulou3. 1. 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. 2. Genetic Metabolic Disorders Research Unit, Kids Research Institute, Children's Hospital at Westmead, Sydney, NSW, Australia. 3. 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.
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. Crown
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. Crown
Authors: Roeltje R Maas; Adela Della Marina; Arjan P M de Brouwer; Ron A Wevers; Richard J Rodenburg; Saskia B Wortmann Journal: JIMD Rep Date: 2015-09-27
Authors: Lisa G Riley; Joëlle Rudinger-Thirion; Klaus Schmitz-Abe; David R Thorburn; Ryan L Davis; Juliana Teo; Susan Arbuckle; Sandra T Cooper; Dean R Campagna; Magali Frugier; Kyriacos Markianos; Carolyn M Sue; Mark D Fleming; John Christodoulou Journal: JIMD Rep Date: 2015-11-05
Authors: Emanuele Monda; Marta Rubino; Michele Lioncino; Francesco Di Fraia; Roberta Pacileo; Federica Verrillo; Annapaola Cirillo; Martina Caiazza; Adelaide Fusco; Augusto Esposito; Fabio Fimiani; Giuseppe Palmiero; Giuseppe Pacileo; Paolo Calabrò; Maria Giovanna Russo; Giuseppe Limongelli Journal: Front Pediatr Date: 2021-02-25 Impact factor: 3.569
Authors: Ahmad Alodaib; Nara Sobreira; Wendy A Gold; Lisa G Riley; Nicole J Van Bergen; Meredith J Wilson; Bruce Bennetts; David R Thorburn; Corinne Boehm; John Christodoulou Journal: Eur J Hum Genet Date: 2016-10-19 Impact factor: 5.351