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. 2013 Jun;109(2):125-31.
doi: 10.1016/j.ymgme.2013.03.020. Epub 2013 Apr 6.

White matter integrity and executive abilities in individuals with phenylketonuria

Jo Ann V Antenor-Dorsey  1 , Tamara Hershey, Jerrel Rutlin, Joshua S Shimony, Robert C McKinstry, Dorothy K Grange, Shawn E Christ, Desirée A White
Affiliations

White matter integrity and executive abilities in individuals with phenylketonuria

Jo Ann V Antenor-Dorsey et al. Mol Genet Metab. 2013 Jun.

Abstract

Previous studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes are poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU.

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Figures

Figure 1
Figure 1
Diffusion tensor imaging (DTI) voxel-wise findings comparing PKU and control groups after controlling for age. Notes: Green = TBSS skeleton; Red = Between-group difference p <.01; Yellow = Between-group difference p <.05.
Figure 2
Figure 2
Relationship between mean diffusivity (MD) voxel-wise findings and phenylalanine (Phe) level for the PKU group after controlling for age. Notes: Green = TBSS skeleton; Red = Between-group difference p <.01; Yellow = Between-group difference p <.05.
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