title: Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study.
abstract: BACKGROUND
  Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism. The main purpose of this retrospective cohort study was to identify prevalence of inherited neurotransmitter disorders.
  
  
  METHODS
  This retrospective cohort study does not have inclusion criteria; rather included all patients who underwent cerebrospinal fluid (CSF) homovanillic and 5-hydroxyindol acetic acid measurements. Patients with CSF neurotransmitter investigations suggestive of an inherited neurotransmitter disorder and patients with normal or non-diagnostic CSF neurotransmitter investigations underwent direct sequencing of single gene disorders.
  
  
  RESULTS
  There were 154 patients between October 2004 and July 2013. Four patients were excluded due to their diagnosis prior to this study dates. Two major clinical feature categories of patients who underwent lumbar puncture were movement disorders or epilepsy in our institution. Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients).
  
  
  CONCLUSIONS
  Prevalence of inherited neurotransmitter disorders was 4% in our retrospective cohort study. Eight out of the 150 patients (5.3%) had one of the treatable inherited metabolic disorders with favorable short-term neurodevelopmental outcomes, highlighting the importance of an early and specific diagnosis. Whole exome or genome sequencing might shed light to unravel underlying genetic defects of new inherited neurotransmitter disorders in near future.
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. saadet.mahmutoglu@sickkids.ca.|Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada. saadet.mahmutoglu@sickkids.ca.|Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, Genetic and Genome Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada. saadet.mahmutoglu@sickkids.ca.
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. sarah.sidky@sickkids.ca.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sidky
authors.affiliation: Medical Neurogenetics, LLC, Atlanta, GA, USA. khyland@mnglab.com.
authors.forename: Keith
authors.initials: K
authors.lastname: Hyland
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. jaina.patel@sickkids.ca.
authors.forename: Jaina
authors.initials: J
authors.lastname: Patel
authors.affiliation: Division of Neurology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. elizabeth.donner@sickkids.ca.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Donner
authors.affiliation: Division of Neurology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. william.logan@sickkids.ca.
authors.forename: William
authors.initials: W
authors.lastname: Logan
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. roberto.mendoza@sickkids.ca.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.affiliation: Division of Neurology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. mahendranath.moharir@sickkids.ca.
authors.forename: Mahendranath
authors.initials: M
authors.lastname: Moharir
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. julian.raiman@sickkids.ca.
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. andreas.schulze@sickkids.ca.|Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada. andreas.schulze@sickkids.ca.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. komudi.siriwardena@sickkids.ca.
authors.forename: Komudi
authors.initials: K
authors.lastname: Siriwardena
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. grace.yoon@sickkids.ca.|Division of Neurology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. grace.yoon@sickkids.ca.
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Biochemical Genetics Laboratory, Department of Laboratory Medicine, University of Toronto, The Hospital for Sick Children, Toronto, Canada. lianna.kyriakopoulou@sickkids.ca.
authors.forename: Lianna
authors.initials: L
authors.lastname: Kyriakopoulou
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020821:Dystonic Disorders / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D009069:Movement Disorders / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult