White matter integrity and executive abilities in individuals with phenylketonuria

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 is 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.

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

“…More rarely, significant relationships have been shown between white matter integrity and cognition in individuals with PKU (Peng et al 2004;Antenor-Dorsey et al 2013). This is somewhat surprising, as compromised white matter integrity has been related to poorer cognition in many other neurological disorders (Chiaravalloti and DeLuca 2008).…”

“…Our knowledge of relationships between DTI findings and cognition is quite limited, but the three relevant studies to date point to associations between MD across a range of brain regions and IQ (Peng et al 2004(Peng et al , 2013Antenor-Dorsey et al 2013). There is, however, no research in which the interplay among white matter integrity, cognition, and Phe control has been modeled within a single study.…”

Is BRIEF a useful instrument in day to day care of patients with phenylketonuria?

“…Problems with EF can express themselves in decreased concentration, learning problems, impulsivity, and inappropriate behavior due to alterations in the prefrontal cortex and associated brain regions [11][12][13]. An article of Waisbren and White in this journal suggested the Behavior Rating Inventory of Executive Function (BRIEF) as a reliable screening method to identify and monitor aspects of daily executive dysfunctioning in patients with PKU [14].…”

Neuropsychological assessment among children and adolescents with phenylketonuria and hyperphenylalaninemia and its relationship with plasma phenylalanine levels

“…13,23 Scores in tests for executive functions have a negative relationship with plasma phenylalanine values. 24,25 Among our patients, a trend can be observed towards a negative relationship among most of the evaluated executive functions and concurrent phenylalanine values along patients' lives.…”