Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?
Аутори
van Vliet, Daniquevan Wegberg, Annemiek M. J.
Ahring, Kirsten
Bik-Multanowski, Miroslaw
Casas, Kari
Didycz, Bozena
Đorđević, Maja
Hertecant, Jozef L.
Leuzzi, Vincenzo
Mathisen, Per
Nardecchia, Francesca
Powell, Kimberly K.
Rutsch, Frank
Stojiljković, Maja
Trefz, Fritz K.
Usurelu, Natalia
Wilson, Callum
van Karnebeek, Clara D.
Hanley, William B.
van Spronsen, Francjan J.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these "unusual" PKU patients show that the clas...sical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations.
Кључне речи:
untreated / phenylketonuria / outcome / late-treated / inter-individual differences / brain vulnerabilityИзвор:
Nutrients, 2019, 11, 11Издавач:
- MDPI, Basel
DOI: 10.3390/nu11112572
ISSN: 2072-6643
PubMed: 31731404
WoS: 000502274600023
Scopus: 2-s2.0-85074474244
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - van Vliet, Danique AU - van Wegberg, Annemiek M. J. AU - Ahring, Kirsten AU - Bik-Multanowski, Miroslaw AU - Casas, Kari AU - Didycz, Bozena AU - Đorđević, Maja AU - Hertecant, Jozef L. AU - Leuzzi, Vincenzo AU - Mathisen, Per AU - Nardecchia, Francesca AU - Powell, Kimberly K. AU - Rutsch, Frank AU - Stojiljković, Maja AU - Trefz, Fritz K. AU - Usurelu, Natalia AU - Wilson, Callum AU - van Karnebeek, Clara D. AU - Hanley, William B. AU - van Spronsen, Francjan J. PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1224 AB - Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these "unusual" PKU patients show that the classical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations. PB - MDPI, Basel T2 - Nutrients T1 - Untreated PKU Patients without Intellectual Disability: What Do They Teach Us? IS - 11 VL - 11 DO - 10.3390/nu11112572 ER -
@article{ author = "van Vliet, Danique and van Wegberg, Annemiek M. J. and Ahring, Kirsten and Bik-Multanowski, Miroslaw and Casas, Kari and Didycz, Bozena and Đorđević, Maja and Hertecant, Jozef L. and Leuzzi, Vincenzo and Mathisen, Per and Nardecchia, Francesca and Powell, Kimberly K. and Rutsch, Frank and Stojiljković, Maja and Trefz, Fritz K. and Usurelu, Natalia and Wilson, Callum and van Karnebeek, Clara D. and Hanley, William B. and van Spronsen, Francjan J.", year = "2019", abstract = "Phenylketonuria (PKU) management is aimed at preventing neurocognitive and psychosocial dysfunction by keeping plasma phenylalanine concentrations within the recommended target range. It can be questioned, however, whether universal plasma phenylalanine target levels would result in optimal neurocognitive outcomes for all patients, as similar plasma phenylalanine concentrations do not seem to have the same consequences to the brain for each PKU individual. To better understand the inter-individual differences in brain vulnerability to high plasma phenylalanine concentrations, we aimed to identify untreated and/or late-diagnosed PKU patients with near-normal outcome, despite high plasma phenylalanine concentrations, who are still alive. In total, we identified 16 such cases. While intellectual functioning in these patients was relatively unaffected, they often did present other neurological, psychological, and behavioral problems. Thereby, these "unusual" PKU patients show that the classical symptomatology of untreated or late-treated PKU may have to be rewritten. Moreover, these cases show that a lack of intellectual dysfunction despite high plasma phenylalanine concentrations does not necessarily imply that these high phenylalanine concentrations have not been toxic to the brain. Also, these cases may suggest that different mechanisms are involved in PKU pathophysiology, of which the relative importance seems to differ between patients and possibly also with increasing age. Further research should aim to better distinguish PKU patients with respect to their cerebral effects to high plasma phenylalanine concentrations.", publisher = "MDPI, Basel", journal = "Nutrients", title = "Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?", number = "11", volume = "11", doi = "10.3390/nu11112572" }
van Vliet, D., van Wegberg, A. M. J., Ahring, K., Bik-Multanowski, M., Casas, K., Didycz, B., Đorđević, M., Hertecant, J. L., Leuzzi, V., Mathisen, P., Nardecchia, F., Powell, K. K., Rutsch, F., Stojiljković, M., Trefz, F. K., Usurelu, N., Wilson, C., van Karnebeek, C. D., Hanley, W. B.,& van Spronsen, F. J.. (2019). Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?. in Nutrients MDPI, Basel., 11(11). https://doi.org/10.3390/nu11112572
van Vliet D, van Wegberg AMJ, Ahring K, Bik-Multanowski M, Casas K, Didycz B, Đorđević M, Hertecant JL, Leuzzi V, Mathisen P, Nardecchia F, Powell KK, Rutsch F, Stojiljković M, Trefz FK, Usurelu N, Wilson C, van Karnebeek CD, Hanley WB, van Spronsen FJ. Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?. in Nutrients. 2019;11(11). doi:10.3390/nu11112572 .
van Vliet, Danique, van Wegberg, Annemiek M. J., Ahring, Kirsten, Bik-Multanowski, Miroslaw, Casas, Kari, Didycz, Bozena, Đorđević, Maja, Hertecant, Jozef L., Leuzzi, Vincenzo, Mathisen, Per, Nardecchia, Francesca, Powell, Kimberly K., Rutsch, Frank, Stojiljković, Maja, Trefz, Fritz K., Usurelu, Natalia, Wilson, Callum, van Karnebeek, Clara D., Hanley, William B., van Spronsen, Francjan J., "Untreated PKU Patients without Intellectual Disability: What Do They Teach Us?" in Nutrients, 11, no. 11 (2019), https://doi.org/10.3390/nu11112572 . .