title: Neurophysiological profile of peripheral neuropathy associated with childhood mitochondrial disease.
abstract: Peripheral nerve involvement is common in mitochondrial disease but often unrecognised due to the prominent central nervous system features. Identification of the underlying neuropathy may assist syndrome classification, targeted genetic testing and rehabilitative interventions.
  
  
  
  Clinical data and the results of nerve conduction studies were obtained retrospectively from the records of four tertiary children's hospital metabolic disease, neuromuscular or neurophysiology services. Nerve conductions studies were also performed prospectively on children attending a tertiary metabolic disease service. Results were classified and analysed according to the underlying genetic cause.
  
  
  
  Nerve conduction studies from 27 children with mitochondrial disease were included in the study (mitochondrial DNA (mtDNA) - 7, POLG - 7, SURF1 - 10, PDHc deficiency - 3). Four children with mtDNA mutations had a normal study while three had mild abnormalities in the form of an axonal sensorimotor neuropathy when not acutely unwell. One child with MELAS had a severe acute axonal motor neuropathy during an acute stroke-like episode that resolved over 12months. Five children with POLG mutations and disease onset beyond infancy had a sensory ataxic neuropathy with an onset in the second decade of life, while the two infants with POLG mutations had a demyelinating neuropathy. Seven of the 10 children with SURF1 mutations had a demyelinating neuropathy. All three children with PDHc deficiency had an axonal sensorimotor neuropathy. Unlike CMT, the neuropathy associated with mitochondrial disease was not length-dependent.
  
  
  
  This is the largest study to date of peripheral neuropathy in genetically- classified childhood mitochondrial disease. Characterising the underlying neuropathy may assist with the diagnosis of the mitochondrial syndrome and should be an integral part of the assessment of children with suspected mitochondrial disease.
authors.affiliation: Institute for Neuroscience and Muscle Research and T.Y. Nelson Department of Neurology & Neurosurgery, The Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia. Electronic address: manoj.menezes@health.nsw.gov.au.
authors.forename: Manoj P
authors.initials: MP
authors.lastname: Menezes
authors.affiliation: Mitochondrial Research Group, Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK; Metabolic Unit, Great Ormond Street Hospital, London, UK.
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia; Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Bhattacharya
authors.affiliation: Department of Neurology, Women's and Children's Hospital, North Adelaide, Australia.
authors.forename: Damian
authors.initials: D
authors.lastname: Clark
authors.affiliation: Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia; Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.affiliation: Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia; Western Sydney Genetics Program, Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ellaway
authors.affiliation: Discipline of Paediatrics, School of Women's and Children's Health, UNSW Medicine, The University of New South Wales, Sydney, Australia; Department of Neurology, Sydney Children's Hospital, Sydney, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Farrar
authors.affiliation: Department of Clinical Neurophysiology, Great Ormond Street Hospital, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Pitt
authors.affiliation: Department of Neurology, Sydney Children's Hospital, Sydney, Australia.
authors.forename: Hugo
authors.initials: H
authors.lastname: Sampaio
authors.affiliation: Department Paediatrics, Royal Hobart Hospital, Hobart, Australia.
authors.forename: Tyson L
authors.initials: TL
authors.lastname: Ware
authors.affiliation: Mitochondrial Research Group, Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK; Metabolic Unit, Great Ormond Street Hospital, London, UK.
authors.forename: Yehani
authors.initials: Y
authors.lastname: Wedatilake
authors.affiliation: Victorian Clinical Genetics Services, Royal Children's Hospital, Melbourne, Australia; Murdoch Childrens Research Institute, Melbourne, Victoria & Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Thorburn
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Victoria & Department of Paediatrics, University of Melbourne, Melbourne, Australia; Children's Neurosciences Centre, The Royal Children's Hospital, Melbourne, Australia.
authors.forename: Monique M
authors.initials: MM
authors.lastname: Ryan
authors.affiliation: Institute for Neuroscience and Muscle Research and T.Y. Nelson Department of Neurology & Neurosurgery, The Children's Hospital at Westmead, Sydney, Australia; Discipline of Paediatrics and Child Health, The Children's Hospital at Westmead Clinical School, The University of Sydney, Sydney, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Ouvrier
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D028361:Mitochondrial Diseases / Q000150:complications* / Q000473:pathology*; D009431:Neural Conduction; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology*; D011446:Prospective Studies; D012189:Retrospective Studies; D062606:Tertiary Care Centers; D055815:Young Adult
keywords: Childhood; Demyelinating; Mitochondrial DNA; Mitochondrial disease; Neuropathy