Abstract
BACKGROUND: Pegvaliase has allowed many adults with phenylketonuria (PKU) to achieve acceptable blood Phe control while eating an unrestricted diet. However, little is known about potential differences in nutritional status and eating behaviors after transitioning from a phenylalanine (Phe)-restricted to an unrestricted diet. Here we assessed change in nutritional status in adults with early-treated PKU who were consuming a Phe-restricted diet (intact protein ≤0.8 g/kg/day) prior to starting pegvaliase. METHODS: A 15-month, prospective, longitudinal study to assess change in anthropometrics, dietary intake, laboratory indices of nutritional status, bone mineral density (BMD), body composition, measured resting energy expenditure (REE), and eating behaviors between baseline and Month 15. RESULTS: Eleven adults (n = 7 female) aged 19.5-52.9 years completed the study. Six participants had a substantial blood Phe reduction (responders) and five participants had a modest blood Phe reduction (partial responders) by Month 15. Intact protein intake increased by an average of 49.4 g/day and 26.7 g/day in responders and partial responders, respectively. Plasma concentrations of most vitamins, minerals, and essential fatty acids assessed were normal, though micronutrient intakes decreased as participants decreased or discontinued PKU medical food(s). Responders had a more variable change in body mass index (BMI) and lean mass index (LMI) compared to partial responders, though there were no clear trends in BMD or body composition changes. Total protein intake was positively correlated with LMI. Responders, but not partial responders, self-reported increased in enjoyment of food and decreased food neophobia, uncontrolled eating, and emotional eating. DISCUSSION: Participants transitioning to an unrestricted diet while on pegvaliase maintained adequate nutritional status overall with no clinically significant changes in cardiovascular or glycemic markers. Responders reported improvements in eating behaviors, including reduced food neophobia, uncontrolled eating, and emotional eating, and increased enjoyment of food. There were no consistent trends in BMD, body composition, or BMI changes. A larger sample size and longer follow-up period are needed to further assess potential changes.