Abstract
Background/objectives
Phenylketonuria (PKU) is a rare autosomal recessive metabolic disorder resulting from a deficiency in phenylalanine hydroxylase (PAH) enzyme activity. This systematic literature review (SLR) aims to synthesize the available evidence on the economic and humanistic burden of PKU on patients and their caregivers.Methods
A comprehensive SLR was conducted using PubMed, Embase, Cochrane Library, International Prospective Register of Systematic Reviews (PROSPERO), EconLit, and the Cost-Effectiveness Analysis (CEA) Registry, from database inception to June 2026. Eligible studies were published in English, included individuals diagnosed with PAH deficiency (including PKU) and/or their caregivers, and reported original data on either the economic or humanistic burden of the condition.Results
Of 2131 records identified, 1330 were screened after deduplication, and 313 underwent full-text review. A total of 130 studies were included, with 44 reporting on economic burden and 87 covering humanistic burden-related outcomes. The economic burden of dietary management was substantial, with mean per patient per year (PPPY) costs ranging from US$1634 to US$35,946, and an estimated 233-359 h PPPY dedicated to diet-related activities. Humanistic burden was also significant; the long-term metabolic control significantly influenced multiple domains of health-related quality of life (HRQoL). In a study involving adults with PKU (n = 88), dietary protein restriction was found to be negatively associated with HRQoL (Rp = 0.265, p Conclusions
Findings underscore the substantial financial, time, and psychological burden of PKU, particularly in relation to dietary management.