title: Brain white matter volume abnormalities in Lesch-Nyhan disease and its variants.
abstract: OBJECTIVE
  We sought to examine brain white matter abnormalities based on MRI in adults with Lesch-Nyhan disease (LND) or an attenuated variant (LNV) of this rare, X-linked neurodevelopmental disorder of purine metabolism.
  
  
  METHODS
  In this observational study, we compared 21 adults with LND, 17 with LNV, and 33 age-, sex-, and race-matched healthy controls using voxel-based morphometry and analysis of covariance to identify white matter volume abnormalities in both patient groups.
  
  
  RESULTS
  Patients with classic LND showed larger reductions of white (26%) than gray (17%) matter volume relative to healthy controls. Those with LNV showed comparable reductions of white (14%) and gray (15%) matter volume. Both patient groups demonstrated reduced volume in medial inferior white matter regions. Compared with LNV, the LND group showed larger reductions in inferior frontal white matter adjoining limbic and temporal regions and the motor cortex. These regions likely include such long association fibers as the superior longitudinal and uncinate fasciculi.
  
  
  CONCLUSIONS
  Despite earlier reports that LND primarily involves the basal ganglia, this study reveals substantial white matter volume abnormalities. Moreover, white matter deficits are more severe than gray matter deficits in classic LND, and also characterize persons with LNV. The brain images acquired for these analyses cannot precisely localize white matter abnormalities or determine whether they involve changes in tract orientation or anisotropy. However, clusters of reduced white matter volume identified here affect regions that are consistent with the neurobehavioral phenotype.
authors.affiliation: From the Departments of Psychiatry and Behavioral Sciences (D.J.S., T.D.V., J.C.H.) and Neurology (M.V., B.G.), and Russell H. Morgan Department of Radiology and Radiological Science (D.J.S., T.D.V.), The Johns Hopkins University School of Medicine; Department of Cognitive Science (B.G.), The Johns Hopkins University, Baltimore, MD; and Departments of Neurology, Human Genetics, and Pediatrics (H.A.J.), Emory University School of Medicine, Atlanta, GA. dschret@jhmi.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schretlen
authors.affiliation: From the Departments of Psychiatry and Behavioral Sciences (D.J.S., T.D.V., J.C.H.) and Neurology (M.V., B.G.), and Russell H. Morgan Department of Radiology and Radiological Science (D.J.S., T.D.V.), The Johns Hopkins University School of Medicine; Department of Cognitive Science (B.G.), The Johns Hopkins University, Baltimore, MD; and Departments of Neurology, Human Genetics, and Pediatrics (H.A.J.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Mark
authors.initials: M
authors.lastname: Varvaris
authors.affiliation: From the Departments of Psychiatry and Behavioral Sciences (D.J.S., T.D.V., J.C.H.) and Neurology (M.V., B.G.), and Russell H. Morgan Department of Radiology and Radiological Science (D.J.S., T.D.V.), The Johns Hopkins University School of Medicine; Department of Cognitive Science (B.G.), The Johns Hopkins University, Baltimore, MD; and Departments of Neurology, Human Genetics, and Pediatrics (H.A.J.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Vannorsdall
authors.affiliation: From the Departments of Psychiatry and Behavioral Sciences (D.J.S., T.D.V., J.C.H.) and Neurology (M.V., B.G.), and Russell H. Morgan Department of Radiology and Radiological Science (D.J.S., T.D.V.), The Johns Hopkins University School of Medicine; Department of Cognitive Science (B.G.), The Johns Hopkins University, Baltimore, MD; and Departments of Neurology, Human Genetics, and Pediatrics (H.A.J.), Emory University School of Medicine, Atlanta, GA.
authors.forename: Barry
authors.initials: B
authors.lastname: Gordon
authors.affiliation: From the Departments of Psychiatry and Behavioral Sciences (D.J.S., T.D.V., J.C.H.) and Neurology (M.V., B.G.), and Russell H. Morgan Department of Radiology and Radiological Science (D.J.S., T.D.V.), The Johns Hopkins University School of Medicine; Department of Cognitive Science (B.G.), The Johns Hopkins University, Baltimore, MD; and Departments of Neurology, Human Genetics, and Pediatrics (H.A.J.), Emory University School of Medicine, Atlanta, GA.
authors.forename: James C
authors.initials: JC
authors.lastname: Harris
authors.affiliation: From the Departments of Psychiatry and Behavioral Sciences (D.J.S., T.D.V., J.C.H.) and Neurology (M.V., B.G.), and Russell H. Morgan Department of Radiology and Radiological Science (D.J.S., T.D.V.), The Johns Hopkins University School of Medicine; Department of Cognitive Science (B.G.), The Johns Hopkins University, Baltimore, MD; and Departments of Neurology, Human Genetics, and Pediatrics (H.A.J.), Emory University School of Medicine, Atlanta, GA.
authors.forename: H A
authors.initials: HA
authors.lastname: Jinnah
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007926:Lesch-Nyhan Syndrome / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology; D009929:Organ Size; D013702:Temporal Lobe / Q000473:pathology; D066127:White Matter / Q000473:pathology*; D055815:Young Adult