Phenylalanine Tolerance over Time in Phenylketonuria: A Systematic Review and Meta-Analysis

In phenylketonuria (PKU), natural protein tolerance is defined as the maximum intake maintaining a blood phenylalanine (Phe) concentration within target therapeutic range. Tolerance affected by several factors, and it may differ throughout person’s lifespan. Data on lifelong Phe/natural are limited mostly reported in studies with low subject numbers. This systematic review aimed to investigate how changes from birth adulthood well-controlled patients PKU Phe-restricted diet. Five electronic databases were searched for articles published until July 2020. From total of 1334 results, 37 met eligibility criteria (n = 2464 patients), 18 included meta-analysis. The mean Phe (mg/day) (g/day) gradually increased 6 y (at age months, was 267 mg/day, 5.4 g/day; at 5 y, 377 8.9 g/day). However, an increase more apparent beginning late childhood >1.5-fold that early childhood. During pubertal growth spurt, protein/Phe approximately three times higher than first year life, reaching 709 mg/day g/day. Post adolescence, pooled analysis could only be performed intake. reached its highest (32.4 g/day) point 17 remained consistent (31.6 adulthood, but data available. results meta-analysis showed (expressed mg or g per day) increases age, particularly puberty, reaches level end adolescence. needs interpreted caution available adult patients. There also high degree heterogeneity between due differences sample size, severity PKU, levels control.