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. 2017 Mar;31(3):242-254.
doi: 10.1037/neu0000336.

The impact of phenylalanine levels on cognitive outcomes in adults with phenylketonuria: Effects across tasks and developmental stages

Cristina Romani  1 , Liana Palermo  1 , Anita MacDonald  2 , Ellie Limback  1 , S Kate Hall  3 , Tarekegn Geberhiwot  4
Affiliations

The impact of phenylalanine levels on cognitive outcomes in adults with phenylketonuria: Effects across tasks and developmental stages

Cristina Romani et al. Neuropsychology. 2017 Mar.

Abstract

Objective: Phenylketonuria (PKU) is due to an inability to metabolize the amino acid phenylalanine (Phe), leading to its accumulation in the brain. Phe levels can be controlled following a protein-free diet, but cognitive impairments are still present. A number of questions remain to be answered related to which type of metabolic control is important, the age when it is important, the cognitive functions which are most affected and, the best tests to use to monitor cognitive health.

Method: We investigated the impact of metabolic control at different ages on cognitive performance in 37 early treated adults with PKU.

Results: (a) Phe variation was as associated to performance as average Phe showing that stable dietary control is as important as strict control; (b) For some tasks, current and adult Phe were stronger predictors of performance than childhood or adolescent Phe, showing the importance of a strict diet even in adulthood; and (c) The relationship between performance and Phe levels varied depending on time and cognitive domain. For some functions (sustained attention, visuomotor coordination), Phe at the time of testing was the best predictor. While for other functions (visual attention, executive functions) there was a diminishing or stable relationship across time.

Conclusion: Results show the importance of selecting the right tasks to monitor outcomes across ages, but also that the impact of bio-chemical disruptions is different for different functions, at different ages. We show how inherited metabolic diseases offer us a unique vantage point to inform our understanding of brain development and functioning. (PsycINFO Database Record

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Figures

Figure 1
Figure 1
Comparison of cognitive abilities in lower- and higher-Phe phenylketonuria groups. Results are in z scores from the control group. Higher z scores always indicate worse performance. The asterisks on the lower-Phe group indicate a significant difference with controls; the asterisks on the higher-Phe group refer to a significant difference with the lower-Phe groups. RT = reaction time. * p < 0.05. ** p < 0.01. See the online article for the color version of this figure.
Figure 2
Figure 2
Correlations by cognitive domain and metabolic control as average Phe. EF = executive functions; STM = short-term memory; RVP = Rapid visual information processing. See the online article for the color version of this figure.
Figure 2
Figure 2
Correlations by cognitive domain and metabolic control as average Phe. EF = executive functions; STM = short-term memory; RVP = Rapid visual information processing. See the online article for the color version of this figure.
Figure 3
Figure 3
Correlations between current Phe and cognitive performance assessed by speed and accuracy measures. STM = short-term memory; EF = executive functions. See the online article for the color version of this figure.
See this image and copyright information in PMC

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