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. 2017:33:41-47.
doi: 10.1007/8904_2016_579. Epub 2016 Jul 22.

Brain White Matter Integrity Mediates the Relationship Between Phenylalanine Control and Executive Abilities in Children with Phenylketonuria

Anna Hood  1 , Jerrel Rutlin  2 , Joshua S Shimony  3 , Dorothy K Grange  4 , Desiree A White  5   4
Affiliations

Brain White Matter Integrity Mediates the Relationship Between Phenylalanine Control and Executive Abilities in Children with Phenylketonuria

Anna Hood et al. JIMD Rep. 2017.

Abstract

We tested the hypothesis that brain white matter integrity mediates the relationship between phenylalanine (Phe) control and executive abilities in children with phenylketonuria (PKU; N = 36). To do so, we examined mean diffusivity (MD) from diffusion tensor imaging (DTI) in two white matter brain regions (posterior parietal-occipital, PPO; centrum semiovale, CSO) and lifetime phenylalanine (Phe) exposure; the executive abilities examined included verbal strategic processing, nonverbal strategic processing, and working memory. Mediation modeling showed that MD in the PPO and CSO mediated the relationship between Phe exposure and nonverbal strategic processing, MD in the CSO mediated the relationship between Phe exposure and verbal strategic processing, and MD in the PPO mediated the relationship between Phe exposure and working memory. These exploratory findings demonstrate the importance of using sophisticated modeling procedures to understand the interplay among metabolic control, neural factors, and functional outcomes in individuals with PKU.

Keywords: Brain; Executive abilities; Mediation; Neuroimaging; Phenylketonuria; White matter.

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Conflict of interest statement

Anna Hood, Jerrel Rutlin, and Joshua Shimony declare that they have no conflict of interest. Desiree White and Dorothy Grange have received research grants from BioMarin Pharmaceutical Inc. and have served as consultants for BioMarin Pharmaceutical Inc.

Figures

Fig. 1
Fig. 1
ROI placement
Fig. 2
Fig. 2
PPO and CSO as mediators of the relationships between mean Phe exposure and executive abilities
See this image and copyright information in PMC

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