Neonatal phenylalanine wash-out in phenylketonuria

Abstract

Phenylketonuria (PKU) is the most common inborn error of amino acids metabolism. PKU management aims to keep as soon as possible blood phenylalanine (Phe), a non-acutely neurotoxic metabolite, within safe ranges through a dietary Phe restriction tailored to individual dietary Phe tolerance. Information on initial neonatal management of PKU, when Phe tolerance is still unknown, is scanty. We reviewed the metabolic data from 304 patients with PAH deficiency detected at newborn screening within the last 37 years. In keeping with the general neonatal management of intoxication-type inborn errors of metabolism, initial management consisted in a Phe wash-out through the exclusive administration of normocaloric Phe-free formulas until normalization of blood Phe. Based on genotype and Phe tolerance assessed at follow-up, 55 patients had classic PKU (18%), 50 mild PKU (17%), and 199 non-PKU hyperphenylalaninemia (HPA) (65%). The duration of Phe wash-out amounted to 7 ± 2 days in classic PKU, 4 ± 2 days in mild PKU, and < 24 h in non-PKU HPA (p < 0.001). After the wash-out, dietary Phe re-introduction and its upwardly titration allowed the assessment of individual metabolic phenotype. During the first 6 years of life, Phe tolerance was stable in classic PKU (~ 200 mg/day) but increased in milder forms, allowing unrestricted diet in non-PKU HPA. Neonatal Phe wash-out in PKU ensures the earliest correction of HPA. This metabolic reset also facilitates the prompt definition of individual Phe tolerance, allowing anticipation of dietary personalization and optimization of longitudinal metabolic control.

Keywords: Hyperphenylalaninemia; Newborn screening; Phenylketonuria; Treatment.