Phenylketonuria as an Adherence Disease

This narrative review explores a novel challenge to adherence in patients with phenylketonuria (PKU). Traditional barriers to maintaining the core of PKU therapy, which involves dietary restrictions, include limited palatability, high costs, difficult access to low-phenylalanine foods, time constraints, and social interference. We propose that adherence may also be hindered by elevated phenylalanine levels in nonadherent patients, leading to cognitive and executive function impairment that reduces their ability to adhere to the diet. Specifically, we hypothesize that the pathophysiological features of PKU create a vicious cycle that exacerbates adherence challenges to the phenylalanine-restricted diet. We therefore propose that PKU may be considered "an adherence disease". The implications of this hypothesis are threefold: 1. Long-term dietary nonadherence is probable among individuals with PKU; 2. the disease itself contributes to the difficulty in adhering to dietary restrictions, potentially alleviating patient guilt; 3. while treatment options depend on individual factors such as disease severity, the most effective approach to mitigating the neurocognitive and psychosocial impacts of PKU is to replace or restore phenylalanine hydroxylase activity.