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

  • Anna Hood
  • Jerrel Rutlin
  • Joshua S. Shimony
  • Dorothy K. Grange
  • Desiree A. White
Research Report
Part of the JIMD Reports book series (JIMD, volume 33)


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.


Brain Executive abilities Mediation Neuroimaging Phenylketonuria White matter 



The authors wish to thank those who participated in our research for their contributions. We also thank Suzin Blankenship and Laurie Sprietsma for their contributions to study management, as well as the physicians and staff of Washington University and Oregon Health & Science University who generously contributed to the study through recruitment and phenylalanine monitoring.


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Anna Hood
    • 1
  • Jerrel Rutlin
    • 2
  • Joshua S. Shimony
    • 3
  • Dorothy K. Grange
    • 4
  • Desiree A. White
    • 1
    • 4
  1. 1.Department of Psychological and Brain SciencesWashington UniversitySt. LouisUSA
  2. 2.Department of PsychiatryWashington UniversitySt. LouisUSA
  3. 3.Mallinckrodt Institute of RadiologyWashington UniversitySt. LouisUSA
  4. 4.Department of PediatricsWashington UniversitySt. LouisUSA

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