caa a22 4500 467932700 CHVBK 20180406152948.0 cr unu---uuuuu 170328e20060201xx s 000 0 eng 10.1007/s10545-006-0096-3 doi (NATIONALLICENCE)springer-10.1007/s10545-006-0096-3 The spectrum of phenylalanine variations under tetrahydrobiopterin load in subjects affected by phenylalanine hydroxylase deficiency [Elektronische Daten] [V. Leuzzi, C. Carducci, C. Carducci, F. Chiarotti, C. Artiola, T. Giovanniello, I. Antonozzi] Summary: A fall in blood phenylalanine (Phe) after tetrahydrobiopterin (BH4) administration is a common trait in phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (McKusick 261600). To explore the extent and biological correlates of this phenomenon we studied: (a) the spectrum of BH4 response in patients with PAH deficiency; (b) the variability of BH4 response according to the severity of the biochemical phenotype; and (c) the variability of the response to BH4 in subjects with the same genotype. Fifty PAH-deficient subjects (age 1 month-35 years) were enrolled for the study (5 with mild hyperphenylalaninaemia (MHPHE), 15 with mild phenylketonuria (MPKU) and 30 with classic phenylketonuria (CPKU) and underwent an identical schedule of blood samplings 24 h before and after oral BH4 challenge (6(R)-BH4, 20 mg/kg per day), leaving Phe intake unchanged. The effect of BH4 on blood Phe concentration was evaluated according to the percent decrease of Phe during the 24 h following the challenge (criterion a), and as variation exceeding the individual variability of blood Phe (criterion b). The number of BH4-responders according to criterion b was 31 (including all the 14 detected by criterion a): 17 out of 30 CPKU (57%), 9 out of 15 MPKU (60%), and all the MHPHE subjects (χ2 = 3.45, df = 2, p = 0.178). The effect of BH4 showed a large interindividual variability unrelated to diagnostic classification, basal value of blood Phe, maximum percentage of Phe reduction, Phe intake, and genotype. Some inconsistencies were found in patients with identical genotype. The first responsive case homozygous for the severe R408W mutation was found. Two new mutations, Y387X and G352C, were identified (the former was BH4-responsive), and the responsiveness of three already reported mutations (R261Q, D338Y, T92I) was substantiated. SSIEM and Springer, 2006 Leuzzi V. Department of Child Neurology and Psychiatry, University of Rome ‘La Sapienza', Via dei Sabelli 108, 00185, Roma, Italy aut Carducci C. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut Chiarotti F. Department of Cell Biology and Neurosciences, National Health Institute, Rome, Italy aut Artiola C. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut Giovanniello T. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut Antonozzi I. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 38-46 0141-8955 29:1<38 2006 29 10545 https://doi.org/10.1007/s10545-006-0096-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10545-006-0096-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Leuzzi V. Department of Child Neurology and Psychiatry, University of Rome ‘La Sapienza', Via dei Sabelli 108, 00185, Roma, Italy aut NATIONALLICENCE 700 1- Carducci C. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut NATIONALLICENCE 700 1- Chiarotti F. Department of Cell Biology and Neurosciences, National Health Institute, Rome, Italy aut NATIONALLICENCE 700 1- Artiola C. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut NATIONALLICENCE 700 1- Giovanniello T. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut NATIONALLICENCE 700 1- Antonozzi I. Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza', Rome aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 29/1(2006-02-01), 38-46 0141-8955 29:1<38 2006 29 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer