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Mol Genet Metab. 2015 Jan;114(1):19-24. doi: 10.1016/j.ymgme.2014.11.007. Epub 2014 Nov 13.

Prolonged exposure to high and variable phenylalanine levels over the lifetime predicts brain white matter integrity in children with phenylketonuria.

Author information

1
Department of Psychology, Washington University, Campus Box 1125, St. Louis, MO 63130, USA.
2
Department of Psychiatry, Washington University School of Medicine, Campus Box 8134, St. Louis, MO 63110, USA.
3
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.
4
Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, St. Louis, MO 63110, USA.
5
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.
6
Department of Pediatrics, Washington University School of Medicine, Campus Box 8116, St. Louis, MO 63110, USA.
7
Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, USA.
8
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.
9
Department of Psychology, Washington University, Campus Box 1125, St. Louis, MO 63130, USA. Electronic address: dawhite@wustl.edu.

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.

KEYWORDS:

Brain; Diffusion tensor imaging; Exposure; Phenylalanine; Phenylketonuria; White matter

PMID:
25481106
PMCID:
PMC4277899
DOI:
10.1016/j.ymgme.2014.11.007
[Indexed for MEDLINE]
Free PMC Article

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