Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10834046 | Molecular Genetics and Metabolism | 2005 | 5 Pages |
Abstract
Patients with tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency may benefit from BH4 therapy instead or in addition to the low-phenylalanine diet. Different loading test protocols are currently used to detect these patients. As a consequence, data on the rate of BH4-responsiveness within patients with mild phenylketonuria (PKU) and/or more severe phenotypes show high variation and a more sensitive and standardised BH4 loading test protocol needs to be defined. We modified the current standard BH4 loading test (20Â mg/kg) to a second administration of 20Â mg/kg after 24Â h and extended blood sampling to 48Â h in 24 patients with PAH deficiency. Using this extended loading test (2Â ÃÂ 20Â mg BH4/kg), the rate of BH4-responsiveness was calculated at 8, 24, and 48Â h after BH4 administration. We defined three groups of patients: “rapid responders” in 10/24 patients (4 mild HPA, 2 mild PKU, 2 moderate PKU, and 2 classic PKU), “moderate responders” in 4/24 patients (4 classic PKU), and “slow responder” in 4/24 patients (4 mild PKU). Six out of 24 patients (1 mild HPA, 1 moderate PKU, and 4 classic PKU) were found to be “non-responder.” Individual phenylalanine profiles show variations in responsiveness at different time points and sampling over 48Â h was more informative than over 24Â h in patients with mild and moderate PKU compared to mild HPA. Analysis of BH4 loading tests in 209 patients with the standard BH4 loading test protocol confirms only minor importance of the 24Â h response: the rate of responsiveness to BH4 after 24Â h was shown to be equal to or even lower than after 8Â h among most phenotypes. However, extension of the BH4 loading test to 48Â h and repeated BH4 administration seems to be useful to detect BH4-responsiveness in more severe phenotypes and allows detecting “slow responders” who may benefit from BH4 therapy.
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Authors
Betina Fiege, Luisa Bonafé, Diana Ballhausen, Matthias Baumgartner, Beat Thöny, David Meili, Laura Fiori, Marcello Giovannini, Nenad Blau,