title: Investigating neurological deficits in carriers and affected patients with ornithine transcarbamylase deficiency.
abstract: BACKGROUND
  Urea cycle disorders are caused by dysfunction in any of the six enzymes and two transport proteins involved in urea biosynthesis. Our study focuses on ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results in a dysfunctional mitochondrial enzyme, which prevents the synthesis of citrulline from carbamoyl phosphate and ornithine. This enzyme deficiency can lead to hyperammonemic episodes and severe cerebral edema. The objective of this study was to use a cognitive battery to expose the cognitive deficits in asymptomatic carriers of OTCD.
  
  
  METHODS
  In total, 81 participants were recruited as part of a larger urea cycle disorder imaging consortium study. There were 25 symptomatic participants (18 female, 7 male, 25.6 year s ± 12.72 years), 20 asymptomatic participants (20 female, 0 male, 37.6 years ± 15.19 years), and 36 healthy control participants (21 female, 15 male, 29.8 years ± 13.39 years). All participants gave informed consent to participate and were then given neurocognitive batteries with standard scores and T scores recorded.
  
  
  RESULTS
  When stratified by symptomatic participant, asymptomatic carrier, and control, the results showed significant differences in measures of executive function (e.g. CTMT and Stroop) and motor ability (Purdue Assembly) between all groups tested. Simple attention, academic measures, language and non-verbal motor abilities showed no significant differences between asymptomatic carriers and control participants, however, there were significant differences between symptomatic and control participant performance in these measures.
  
  
  CONCLUSIONS
  In our study, asymptomatic carriers of OTCD showed no significant differences in cognitive function compared to control participants until they were cognitively challenged with fine motor tasks, measures of executive function, and measures of cognitive flexibility. This suggests that cognitive dysfunction is best measurable in asymptomatic carriers after they are cognitively challenged.
authors.affiliation: Department of Neurogenetics, Children's National Medical Center, Washington D.C., USA; Center for Functional and Molecular Imaging, Georgetown University, Washington D.C., USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Sprouse
authors.affiliation: Department of Neurogenetics, Children's National Medical Center, Washington D.C., USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: King
authors.affiliation: Department of Neurogenetics, Children's National Medical Center, Washington D.C., USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Helman
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington D.C., USA.
authors.forename: Ileana
authors.initials: I
authors.lastname: Pacheco-Colón
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington D.C., USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Shattuck
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington D.C., USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Breeden
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Seltzer
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington D.C., USA.
authors.forename: John W
authors.initials: JW
authors.lastname: VanMeter
authors.affiliation: Department of Neurogenetics, Children's National Medical Center, Washington D.C., USA; Center for Functional and Molecular Imaging, Georgetown University, Washington D.C., USA; George Washington University of Health Sciences, Washington D.C., USA.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009483:Neuropsychological Tests; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000150:complications* / Q000235:genetics*; D011597:Psychomotor Performance; D055815:Young Adult
keywords: Asymptomatic carriers; Cognitive function; Metabolic disease; Ornithine transcarbamylase deficiency; Urea cycle disorders