Background: The clinical severity of phenylalanine hydroxylase deficiency is usually defined by either pre-treatment phenylalanine (Phe) concentration or Phe tolerance at 5 years of age. So far, little is known about the course of Phe tolerance or the ability of both pre-treatment Phe and Phe tolerance at early age to predict Phe tolerance at later age. Aim: This study was conducted to investigate the course of the individual Phe tolerance and to assess the predictive value of both the pre-treatment Phe concentration and Phe tolerance at 1 and 6 months and 1, 2, 3 and 5 years for Phe tolerance at 10 years of age. Method: Data on blood Phe concentration, prescribed Phe intake and weight of 213 early and continuously treated Dutch PKU patients up to 10 years of age were collected. Data acquired under good metabolic control were used in the study. Tolerance was expressed in mg/day and mg/kg per day. Results: Data at 1 and 6 months and at 1, 2, 3 and 5 years of 61, 58, 59, 57, 56 and 59 patients were included for comparison with the Phe tolerance at 10 years. Phe tolerances (mg/kg per day) at 2, 3 and 5 years showed a clear correlation with the tolerance at 10 years of age (r = 0.608, r = 0.725 and r = 0.661). Results for tolerance expressed as mg/day were comparable. Pre-treatment Phe concentrations did not correlate significantly with the tolerance. Conclusion: Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age.,
Journal of Inherited Metabolic Disease
Erasmus MC: University Medical Center Rotterdam

van Spronsen, F.J, van Rijn, M.E, Dorgelo, B, Hoeksma, M, Bosch, A.M, Mulder, M.F, … Verkerk, P.H. (2009). Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU. Journal of Inherited Metabolic Disease, 32(1), 27–31. doi:10.1007/s10545-008-0937-3