Due to a rare metabolic defect, patients suffering from phenylketonuria (PKU) cannot process the amino acid phenylalanine (Phe). A build-up of Phe in the body causes severe brain damage and developmental disorders in children. To avoid this build-up, a low-Phe (i.e. low-protein) diet must be followed in children with PKU. To what extent adult patients with PKU must follow such a strict diet remains unclear to this day. The PICO study investigates the influence of increased Phe levels on the adult brain of patients with PKU. For this purpose, a short-term break in the Phe-free diet is simulated by administering Phe capsules and changes in the brain are examined with the help of neuropsychological tests, structural and functional MRI.