Is Phenylalanine Restricted Dietary Treatment in Phenylketonuria Associated with Disordered Eating: A Systematic...

Background: In phenylketonuria (PKU), the lifelong phenylalanine (Phe)-restricted diet may contribute to altered feeding behaviours and disordered eating. The true prevalence of disordered eating and eating disorders remains uncertain, partly because validated PKU-specific assessment tools are lacking. This systematic review aimed to identify, appraise, and synthesise the evidence on disordered eating and eating disorders in PKU. Methods: Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane) were searched from inception to 24 February 2026. English-language studies reporting disordered eating or eating disorders in early-diagnosed individuals with PKU managed with a Phe-restricted diet, with or without drug therapy, were included. Studies of late- or never-treated patients, pregnancy, lactation, reviews, and preclinical studies were excluded. Two independent reviewers conducted study selection and data extraction. Outcomes included the prevalence of eating disorders, disordered eating behaviours and attitudes, associated factors, and the influence of drug treatment. Findings were synthesised qualitatively, and risk of bias was assessed using the NIH Study Quality Assessment Tools. Results: Twenty-four studies (2928 individuals with PKU) met the inclusion criteria. Most were observational or survey-based. Eating disorders were reported more frequently in PKU (3-13%) than in the general population (n = 4 studies). Common disordered eating features included food neophobia (n = 5 studies), limited food variety (n = 9), food aversion or refusal (n = 5), poor appetite (n = 5), prolonged mealtimes (n = 3), negative parent-child mealtime interactions (n = 6), and specific taste preferences (n = 5). Delayed feeding skill development (n = 6 studies), reduced social eating (n = 6), gastrointestinal symptoms (n = 8), and psychological or neurodevelopmental difficulties (n = 7) were also associated with disordered eating. Early feeding difficulties frequently persisted into adulthood, and longstanding eating behaviours did not consistently improve with pharmaceutical treatment (n = 6 studies). Most studies were rated as fair quality (19/24), with common limitations including small sample sizes, lack of sample-size justification, non-validated assessment tools, and absence of randomised controlled trials. Conclusions: Current evidence suggests that people with PKU experience a greater burden of eating-related difficulties than the general population, although robust estimates of eating disorder prevalence remain lacking. Existing screening tools may misclassify treatment-related dietary behaviours as pathological or fail to identify PKU-specific eating concerns. Development of PKU-specific screening tools could support routine clinical discussions about eating behaviours and the psychosocial impact of dietary treatment, facilitating earlier identification of individuals requiring specialist eating disorder assessment. (Prospero registration: CRD42024539600).