Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria

Despite good control of phenylalanine (Phe) levels during childhood and adolescence, adults with phenylketonuria (PKU) often show abnormalities in the white matter of the brain, which have been associated with poorer cognitive performance. However, whether such a relationship exists with cortical gray matter is still unknown. Therefore, we investigated cortical thickness and surface area in adults with early‐treated PKU and their relationship to cognitive functions and metabolic control. We included 30 adult patients with early‐treated and metabolically well‐controlled PKU (median age: 35.5 years) and 54 healthy controls (median age: 29.3 years). Surface‐based morphometry was derived from T1‐weighted magnetic resonance images using FreeSurfer, and general intelligence, executive functions, and attention were assessed. Concurrent plasma Phe, tyrosine, and tryptophan levels were measured in patients. In addition, Phe levels were collected retrospectively to calculate the index of dietary control. Patients showed a thinner cortex than controls in regions of the bilateral temporal, parietal, and occipital lobes (effect size r = −0.34 to −0.42, p