Francesca Nardecchia1, Flavia Chiarotti2, Claudia Carducci3, Silvia Santagata3, Giulia Valentini1, Antonio Angeloni3, Nenad Blau4, Vincenzo Leuzzi5. 1. Department of Pediatrics, Child Neurology and Psychiatry, SAPIENZA University of Rome, Via dei Sabelli 108, 00185, Rome, Italy. 2. Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. 3. Department of Experimental Medicine, SAPIENZA University of Rome, Viale del Policlinico 155, 00161, Rome, Italy. 4. Dietmar-Hopp-Metabolic Center, University Children's Hospital, Heidelberg, Germany. 5. Department of Pediatrics, Child Neurology and Psychiatry, SAPIENZA University of Rome, Via dei Sabelli 108, 00185, Rome, Italy. vincenzo.leuzzi@uniroma1.it.
Abstract
The tetrahydrobiopterin (BH4) cofactor is essential for the activity of various enzymes, including phenylalanine (Phe) hydroxylase. In phenylketonuria (PKU) patients, who are chronically exposed to high Phe levels, high urinary excretion of BH4 metabolites neopterin and biopterin is observed. The aim of this longitudinal study was to investigate consistence and variability of the urinary excretion of pterins (neopterin and biopterin) in PKU patients in relation to age and concomitant blood Phe and tyrosine levels. The study was based on the result of 274 pterin examinations (3-13 exams per subject) performed in 47 PKU patients (aged 6 days to 37 years). Multivariate analysis showed that urinary biopterin and neopterin excretion was affected by age and concomitant blood Phe concentration. The influence of blood Phe on both biopterin and neopterin levels was greater in patients younger than 4 months. Later on, interindividual variability was higher than intraindividual variability for both biopterin and neopterin. CONCLUSION: Common metabolic (blood Phe levels) and individual (age) factors implicated in the assessment of PKU outcome account only marginally and transiently for the variability of neopterin and biopterin excretion in PKU patients. Other unknown homeostatic factors may probably affect the individual response to chronically elevated Phe levels. What is Known: • In PKU patients, a high urinary excretion of biopterin and neopterin is found. • Biopterin and neopterin excretion is influenced by age and phenylalanine levels. W hat is New: • Blood phenylalanine concentration is the major determinant on pterin excretion in PKU patients in the first months of life. • In older PKU patients, the influence of phenylalanine on pterin excretion is less prominent.
The tetrahydrobiopterin (BH4) cofactor is essential for the activity of various enzymes, including phenylalanine (Phe) hydroxylase. In phenylketonuria (PKU) patients, who are chronically exposed to high Phe levels, high urinary excretion of BH4 metabolites neopterin and biopterin is observed. The aim of this longitudinal study was to investigate consistence and variability of the urinary excretion of pterins (neopterin and biopterin) in PKUpatients in relation to age and concomitant blood Phe and tyrosine levels. The study was based on the result of 274 pterin examinations (3-13 exams per subject) performed in 47 PKUpatients (aged 6 days to 37 years). Multivariate analysis showed that urinary biopterin and neopterin excretion was affected by age and concomitant blood Phe concentration. The influence of blood Phe on both biopterin and neopterin levels was greater in patients younger than 4 months. Later on, interindividual variability was higher than intraindividual variability for both biopterin and neopterin. CONCLUSION: Common metabolic (blood Phe levels) and individual (age) factors implicated in the assessment of PKU outcome account only marginally and transiently for the variability of neopterin and biopterin excretion in PKUpatients. Other unknown homeostatic factors may probably affect the individual response to chronically elevated Phe levels. What is Known: • In PKUpatients, a high urinary excretion of biopterin and neopterin is found. • Biopterin and neopterin excretion is influenced by age and phenylalanine levels. W hat is New: • Blood phenylalanine concentration is the major determinant on pterin excretion in PKUpatients in the first months of life. • In older PKUpatients, the influence of phenylalanine on pterin excretion is less prominent.
Entities:
Keywords:
Biochemical variability in PKU; Biopterin; Neopterin; Phenylketonuria; Tetrahydrobiopterin (BH4)
Authors: Danique van Vliet; Karen Anjema; Rianne Jahja; Martijn J de Groot; Geertje B Liemburg; M Rebecca Heiner-Fokkema; Eddy A van der Zee; Terry G J Derks; Ido P Kema; Francjan J van Spronsen Journal: Mol Genet Metab Date: 2014-11-15 Impact factor: 4.797
Authors: A Ponzone; O Guardamagna; M Spada; R Ponzone; M Sartore; L Kierat; C W Heizmann; N Blau Journal: Clin Chim Acta Date: 1993-07-16 Impact factor: 3.786