The Economic Burden of Phenylketonuria Among Patients and Their Caregivers: A Systematic Literature Review From a Global Perspective

OBJECTIVES: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder characterized by a deficiency in phenylalanine hydroxylase enzyme activity. This study systematically synthesized the published evidence on the economic burden of PKU.

METHODS: A systematic literature review (SLR) was conducted via PubMed, Embase, Cochrane Library, PROSPERO, EconLit, and CEA Registry, with no starting date limit and up to January 2024. Studies published in English, without geographical restrictions, examining healthcare resource utilization (HCRU), and direct and indirect costs associated with PKU were included. All costs were converted and/or adjusted to 2023 US dollars.

RESULTS: A total of 1,753 records were identified, of which 1,102 were screened after deduplication, and 266 were subsequently reviewed. Thirty-nine studies, including 18 studies for HCRU and 34 studies for costs, met the inclusion criteria. Most of the studies (n=38) focused on patients with PKU, while six studies assessed caregiver burden. Approximately 18,648 patients with PKU and 498 caregivers were examined in this review. The included studies were heterogeneous in design and patient populations covered, resulting in a wide range of reported data. The mean number of hospitalizations per patient per year (PPPY) ranged from 0.12 to 1.18 (5 studies), and the mean length of stay ranged from 4.04-20.0 days PPPY (5 studies). Overall, diet management imposed a significant burden, as mean costs ranged from $1,546 - $ 31,381 PPPY (6 studies), and the mean time spent on diet related activities ranged from 233 to 359 hours PPPY (2 studies). The mean cost of protein substitutes also increased with age (2 years: $7,971; 30 years: $27,292) (1 international study).

CONCLUSIONS: Despite being a rare disease, a substantial body of literature exists for PKU. However, comparability of studies was limited due to the heterogeneity of data. This SLR highlights the significant cost and time burden associated with PKU among patients and caregivers.