title: Prolonged exposure to high and variable phenylalanine levels over the lifetime predicts brain white matter integrity in children with phenylketonuria.
abstract: In this study, we retrospectively examined the microstructural white matter integrity of children with early- and continuously-treated PKU (N=36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure, and standard deviation exposure were the most powerful predictors of widespread microstructural white matter integrity compromise. Findings from the two previously unexamined exposure indices reflected the accumulative effects of elevations and variability in Phe. Given that prolonged exposure to elevated and variable Phe was particularly detrimental to white matter integrity, Phe should be carefully monitored and controlled throughout childhood, without liberalization of Phe control as children with PKU age.
authors.affiliation: Department of Psychology, Washington University, Campus Box 1125, St. Louis, MO 63130, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Hood
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, St. Louis, MO 63110, USA.
authors.forename: Jo Ann V
authors.initials: JA
authors.lastname: Antenor-Dorsey
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, St. Louis, MO 63110, USA.
authors.forename: Jerrel
authors.initials: J
authors.lastname: Rutlin
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, St. Louis, MO 63110, USA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, Campus Box 8111, St. Louis, MO 63110, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Hershey
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, St. Louis, MO 63110, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Shimony
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, St. Louis, MO 63110, USA; Department of Pediatrics, Washington University School of Medicine, Campus Box 8116, St. Louis, MO 63110, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: McKinstry
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, Campus Box 8116, St. Louis, MO 63110, USA.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, USA.
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Christ
authors.affiliation: Department of Pediatrics, Institute on Development and Disability, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR, 97239 USA; Department of Molecular & Medical Genetics, Institute on Development and Disability, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Steiner
authors.affiliation: Department of Psychology, Washington University, Campus Box 1125, St. Louis, MO 63130, USA. Electronic address: dawhite@wustl.edu.
authors.forename: Desiree A
authors.initials: DA
authors.lastname: White
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D059906:Neuroimaging; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood*; D010661:Phenylketonurias / Q000097:blood* / Q000473:pathology*; D012189:Retrospective Studies; D066127:White Matter / Q000473:pathology*
chemical_list: D010649:Phenylalanine
keywords: Brain; Diffusion tensor imaging; Exposure; Phenylalanine; Phenylketonuria; White matter