LAUSR

Purpose: this systematic review aimed to assess the effects of dietary liberalization following tetrahydrobiopterin (BH4) treatment on anthropometric measurements, nutritional biomarkers, quality of life, bone density, mental health and psychosocial functioning, and burden of care in PKU patients. Methods: the PubMed, Cochrane, and Embase databases were searched on 7 April 2022. We included studies that reported on the aforementioned domains before and after dietary liberalization as a result of BH4 treatment in PKU patients. Exclusion criteria were: studies written in a language other than English; studies that only included data of a BH4 loading test; insufficient data for the parameters of interest; and wrong publication type. Both within-subject and between-subject analyses were assessed, and meta-analyses were performed if possible. Results: twelve studies containing 14 cohorts and 228 patients were included. Single studies reported few significant differences. Two out of fifteen primary meta-analyses were significant; BMI was higher in BH4-treated patients versus controls (p = 0.02; standardized mean difference (SMD) (95% confidence interval (CI)) = −0.37 (−0.67, −0.06)), and blood cholesterol concentrations increased after starting BH4 treatment (p = 0.01; SMD (CI) = −0.70 (−1.26, −0.15)). Conclusion: there is no clear evidence that dietary liberalization after BH4 treatment has a positive effect on anthropometric measurements, nutritional biomarkers, or quality of life. No studies could be included for bone density, mental health and psychosocial functioning, and burden of care.