Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients: Does It Improve Outcomes?

Purpose: this systematic review aimed to assess the effects of dietary liberalization following tetrahydrobiopterin (BH ₄ ) 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 BH ₄ treatment in PKU patients. Exclusion criteria were: studies written in a language other than English; studies that only included data of a BH ₄ 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 BH ₄ -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 BH ₄ treatment ( p = 0.01; SMD (CI) = -0.70 (-1.26, -0.15)).
Conclusion: there is no clear evidence that dietary liberalization after BH ₄ 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.