Neonatal phenylalanine wash-out in phenylketonuria
- PDF / 277,831 Bytes
- 5 Pages / 595.276 x 790.866 pts Page_size
- 22 Downloads / 174 Views
ORIGINAL ARTICLE
Neonatal phenylalanine wash-out in phenylketonuria Francesco Porta 1,2 & Alberto Ponzone 1 & Marco Spada 1 Received: 13 January 2020 / Accepted: 9 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 reintroduction 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 Phenylketonuria . Hyperphenylalaninemia . Newborn screening . Treatment
Introduction Phenylketonuria (PKU, OMIM 261,600), due to over 800 mutations variably impairing phenylalanine hydroxylase (PAH, EC 1.14.16.1) activity, is the most common inborn error of amino acids metabolism. Newborn screening enables its pre-symptomatic detection and the prevention of mental retardation due to chronic hyperphenylalaninemia (HPA). Management of PKU aims to keep blood phenylalanine (Phe), a non-acutely neurotoxic metabolite, within safe ranges through a dietary Phe restriction tailored to individual Phe tolerance (Scriver et al. 2001; Blau et al. 2010a, b; Porta et al. 2011a). In spite of a huge literature on PKU (> 7000
* Francesco Porta [email protected] 1
Department of Pediatrics, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy
2
Department of Pediatrics, University of Torino Piazza Polonia 94, Turin 10126, Italy
articles), scarce attention was given to its initial neonatal management, when Phe tolerance is still unknown. A classification of PKU based on pre-treatment blood Phe concentrations (> 1200 µmol/l, classic PKU; 600–1200 µmol/l
Data Loading...
