title: Diffusion tensor imaging detects areas of abnormal white matter microstructure in patients with partial ornithine transcarbamylase deficiency.
abstract: OBJECTIVE
  OTCD, an X-linked disorder, is the most common of the UCDs. Neonatal onset is associated with uniformly poor outcome. Males with late-onset OTCD show deficits in executive function, motor planning, and working memory. A broad phenotype is observed in heterozygous females. A specific neurobehavioral phenotype with white matter dysfunction and impaired attention and working memory has been described. The extent to which the deficits involve specific pathways in the brain is unknown. We hypothesized that DTI would disclose white matter microstructure in OTCD correlating with cognitive deficits.
  
  
  METHODS
  Nineteen adults with partial OTCD and 18 adult control subjects ages 19-59 years participated. MR imaging was performed by using a 3T whole-body scanner. Anisotropy was calculated from the eigenvalues of the diffusion tensor by using the FA metric and was compared between the study and control groups.
  
  
  RESULTS
  FA of the frontal white matter was significantly decreased in subjects, indicating changes in white matter microstructure. There was an inverse relationship between FA and disease severity, but not with age.
  
  
  CONCLUSIONS
  Findings of MR imaging in OTCD are often normal in patients with late-onset disease, heterozygotes, or in those not in hyperammonemic crisis. DTI was more sensitive than FSE T2-weighted imaging for detecting abnormalities in normal-appearing white matter. The extent of abnormality correlated with cognitive deficits. The location of the deficits in the frontal white matter is important because this area connects fibers that are vital to executive function, attention, and working memory.
authors.affiliation: Department of Neurology, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA. agropman@cnmc.org
authors.forename: A L
authors.initials: AL
authors.lastname: Gropman
authors.forename: B
authors.initials: B
authors.lastname: Gertz
authors.forename: K
authors.initials: K
authors.lastname: Shattuck
authors.forename: I L
authors.initials: IL
authors.lastname: Kahn
authors.forename: R
authors.initials: R
authors.lastname: Seltzer
authors.forename: L
authors.initials: L
authors.lastname: Krivitsky
authors.forename: J
authors.initials: J
authors.lastname: Van Meter
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000150:complications* / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000150:complications / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult