BACKGROUND: Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU patients treated with BH(4). SUBJECTS AND METHODS: Based on the review of neonatal BH(4) test results and mutation analysis in 41 PKU patients, 19 were identified as potentially BH(4)-sensitive (9 females, 10 males, age 4-18 years). We analyzed phenylalanine (phe) concentrations in dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL(®)) beginning from 1 year before, during the first 42 days, and after 3 months of BH(4) therapy. RESULTS: Eight BH(4)-sensitive patients increased their phe tolerance (629 ± 476 vs. 2131 ± 1084 mg, p = 0.006) while maintaining good metabolic control (phe concentration in dried blood 283 ± 145 vs. 304 ± 136 μM, p = 1.0). Six of them were able to stop dietary protein restriction entirely. BH(4)-sensitive patients had average HRQoL scores that were comparable to age-matched healthy children. There was no improvement in HRQoL scores after replacing classic dietary treatment with BH(4) supply, although personal reports given by the patients and their parents suggest that available questionnaires are inappropriate to detect aspects relevant to inborn metabolic disorders. DISCUSSION: BH(4) can allow PKU patients to increase their phe consumption significantly or even stop dietary protein restrictions. Unexpectedly, this does not improve HRQoL as assessed with KINDL(®), partly due to high scores even before BH(4) therapy. Specific questionnaires should be developed for inborn metabolic disorders.
BACKGROUND:Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKUpatients treated with BH(4). SUBJECTS AND METHODS: Based on the review of neonatal BH(4) test results and mutation analysis in 41 PKUpatients, 19 were identified as potentially BH(4)-sensitive (9 females, 10 males, age 4-18 years). We analyzed phenylalanine (phe) concentrations in dried blood samples, nutrition protocols, and HRQoL questionnaires (KINDL(®)) beginning from 1 year before, during the first 42 days, and after 3 months of BH(4) therapy. RESULTS: Eight BH(4)-sensitive patients increased their phe tolerance (629 ± 476 vs. 2131 ± 1084 mg, p = 0.006) while maintaining good metabolic control (phe concentration in dried blood 283 ± 145 vs. 304 ± 136 μM, p = 1.0). Six of them were able to stop dietary protein restriction entirely. BH(4)-sensitive patients had average HRQoL scores that were comparable to age-matched healthy children. There was no improvement in HRQoL scores after replacing classic dietary treatment with BH(4) supply, although personal reports given by the patients and their parents suggest that available questionnaires are inappropriate to detect aspects relevant to inborn metabolic disorders. DISCUSSION: BH(4) can allow PKUpatients to increase their phe consumption significantly or even stop dietary protein restrictions. Unexpectedly, this does not improve HRQoL as assessed with KINDL(®), partly due to high scores even before BH(4) therapy. Specific questionnaires should be developed for inborn metabolic disorders.
Authors: Ulrike Mütze; Annika Roth; Johannes F W Weigel; Skadi Beblo; Christoph G Baerwald; Peter Bührdel; Wieland Kiess Journal: J Inherit Metab Dis Date: 2011-02-09 Impact factor: 4.982
Authors: Angel L Pey; Belén Pérez; Lourdes R Desviat; Maria Angeles Martínez; Cristina Aguado; Heidi Erlandsen; Alejandra Gámez; Raymond C Stevens; Matthías Thórólfsson; Magdalena Ugarte; Aurora Martínez Journal: Hum Mutat Date: 2004-11 Impact factor: 4.878
Authors: A J Thompson; I Smith; D Brenton; B D Youl; G Rylance; D C Davidson; B Kendall; A J Lees Journal: Lancet Date: 1990-09-08 Impact factor: 79.321
Authors: Marcel R Zurflüh; Johannes Zschocke; Martin Lindner; François Feillet; Céline Chery; Alberto Burlina; Raymond C Stevens; Beat Thöny; Nenad Blau Journal: Hum Mutat Date: 2008-01 Impact factor: 4.878
Authors: Eva Simon; Martin Schwarz; Judith Roos; Nico Dragano; Max Geraedts; Johannes Siegrist; Gudrun Kamp; Udo Wendel Journal: Health Qual Life Outcomes Date: 2008-03-26 Impact factor: 3.186
Authors: Chiara Cazzorla; Luca Cegolon; Alessandro P Burlina; Andrea Celato; Pamela Massa; Laura Giordano; Giulia Polo; Aurora Daniele; Francesco Salvatore; Alberto B Burlina Journal: BMC Public Health Date: 2014-12-04 Impact factor: 3.295
Authors: Karen Anjema; Margreet van Rijn; Floris C Hofstede; Annet M Bosch; Carla E M Hollak; Estela Rubio-Gozalbo; Maaike C de Vries; Mirian C H Janssen; Carolien C A Boelen; Johannes G M Burgerhof; Nenad Blau; M Rebecca Heiner-Fokkema; Francjan J van Spronsen Journal: Orphanet J Rare Dis Date: 2013-07-10 Impact factor: 4.123