title: Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism.
abstract: OBJECTIVE
  Creatine deficiency may play a role in the neurobiology of autism and may represent a treatable cause of autism. The goal of the study was to ascertain the prevalence of creatine deficiency syndromes (CDSs) in children with autism spectrum disorder (ASD).
  
  
  METHODS
  In a prospective multicenter study, 443 children were investigated after a confirmed diagnosis of ASD. Random spot urine screening for creatine metabolites (creatine, guanidinoacetate, creatinine, and arginine) with liquid chromatography-tandem mass spectrometry and second-tier testing with high-performance liquid chromatography methodology was followed by recall testing in 24-hour urines and confirmatory testing by Sanger-based DNA sequencing of GAMT, GATM, and SLC6A8 genes. Additional diagnostic tests included plasma creatine metabolites and in vivo brain proton magnetic resonance spectroscopy. The creatine metabolites in spot urine in the autism group were compared with 128 healthy controls controlled for age.
  
  
  RESULTS
  In 443 subjects with ASD investigated for CDS, we had 0 events (event: 0, 95% confidence interval 0-0.0068), therefore with 95% confidence the prevalence of CDS is <7 in 1000 children with ASD. The autism and control groups did not vary in terms of creatine metabolites (P > .0125) in urine.
  
  
  CONCLUSIONS
  Our study revealed a very low prevalence of CDS in children with nonsyndromic ASD and no obvious association between creatine metabolites and autism. Unlike our study population, we expect more frequent CDS among children with severe developmental delay, speech impairment, seizures, and movement disorders in addition to impairments in social communication, restricted interests, and repetitive behaviors.
authors.affiliation: Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, Toronto, Ontario, Canada; Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Ontario, Canada; andreas.schulze@sickkids.ca.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Lurie Center for Autism, MassGeneral Hospital, Boston, Massachusetts; Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts;
authors.forename: Margaret
authors.initials: M
authors.lastname: Bauman
authors.affiliation: Colorado University Medical School, Aurora, Colorado; Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, Oregon;
authors.forename: Anne Chun-Hui
authors.initials: AC
authors.lastname: Tsai
authors.affiliation: Colorado University Medical School, Aurora, Colorado;
authors.forename: Ann
authors.initials: A
authors.lastname: Reynolds
authors.affiliation: Department of Paediatrics, University of Toronto, Ontario, Canada; Holland Bloorview Kids Rehabilitation, Toronto, Ontario, Canada;
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.affiliation: Department of Paediatrics, University of Toronto, Ontario, Canada; Holland Bloorview Kids Rehabilitation, Toronto, Ontario, Canada;
authors.forename: Evdokia
authors.initials: E
authors.lastname: Anagnostou
authors.affiliation: Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, Toronto, Ontario, Canada;
authors.forename: Jessie
authors.initials: J
authors.lastname: Cameron
authors.affiliation: Clinical and Translational Science Center, Harvard Medical School, Boston, Massachusetts;
authors.forename: Alixandra A
authors.initials: AA
authors.lastname: Nozzolillo
authors.affiliation: Clinical Research Services, The Hospital for Sick Children, Toronto, Ontario, Canada;
authors.forename: Shiyi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Paediatric Laboratory Medicine, Biochemical Genetics Laboratory, The Hospital for Sick Children, Toronto, Ontario, Canada;
authors.forename: Lianna
authors.initials: L
authors.lastname: Kyriakopoulou
authors.affiliation: Genetics and Genome Biology, Peter Gilgan Center for Research and Learning, Toronto, Ontario, Canada; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Ontario, Canada;
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: Department of Paediatrics, University of Toronto, Ontario, Canada; Surrey Place Center, Toronto, Ontario, Canada.
authors.forename: Alvin
authors.initials: A
authors.lastname: Loh
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D003401:Creatine / Q000172:deficiency*; D003677:Deficiency Diseases / Q000150:complications / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D015995:Prevalence; D011446:Prospective Studies; D013577:Syndrome
chemical_list: D003401:Creatine