Morphometric analysis of gray matter integrity in individuals with early-treated phenylketonuria

• Early-treated PKU associated with decreased parietal & occipital gray matter volume.
• No evidence of PKU-related differences in frontal or temporal gray matter volume.
• Tentative support for link between phe levels and effects on cortical gray matter.

The most widely-reported neurologic finding in individuals with early-treated phenylketonuria (PKU) is abnormality in the white matter of the brain. In contrast, much less is known regarding the impact of PKU on cortical gray matter (GM) structures. Presently, we applied advanced morphometric methods to the analysis of high-resolution structural MRI images from a sample of 19 individuals with early-treated PKU and an age- and gender-matched comparison group of 22 healthy individuals without PKU. Data analysis revealed decreased GM volume in parietal cortex for the PKU group compared with the non-PKU group. A similar trend was observed for occipital GM volume. There was no evidence of group-related differences in frontal or temporal GM volume. Within the PKU group, we also found a significant relationship between blood phenylalanine levels and GM volume for select posterior cortical sub-regions. Taken together with previous research on white matter and gray matter abnormalities in PKU, the present findings point to the posterior cortices as the primary site of neurostructural changes related to early-treated PKU.