TY  - JOUR
AU  - van Vliet, Danique
AU  - van Wegberg, Annemiek M. J.
AU  - Ahring, Kirsten
AU  - Bik-Multanowski, Miroslaw
AU  - Blau, Nenad
AU  - Bulut, Fatma D.
AU  - Casas, Kari
AU  - Didycz, Bozena
AU  - Đorđević, Maja
AU  - Federico, Antonio
AU  - Feillet, Francois
AU  - Gizewska, Maria
AU  - Gramer, Gwendolyn
AU  - Hertecant, Jozef L.
AU  - Hollak, Carla E. M.
AU  - Jorgensen, Jens V.
AU  - Karall, Daniela
AU  - Landau, Yuval
AU  - Leuzzi, Vincenzo
AU  - Mathisen, Per
AU  - Moseley, Kathryn
AU  - Mungan, Neslihan O.
AU  - Nardecchia, Francesca
AU  - Ounap, Katrin
AU  - Powell, Kimberly K.
AU  - Ramachandran, Radha
AU  - Rutsch, Frank
AU  - Setoodeh, Aria
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  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1097
AB  - Background: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. Methods: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations  gt = 1200 mu mol/l; and 3) IQ  gt = 80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. Results: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. Conclusions: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re) present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.
PB  - BMC, London
T2  - Orphanet Journal of Rare Diseases
T1  - Can untreated PKU patients escape from intellectual disability? A systematic review
VL  - 13
DO  - 10.1186/s13023-018-0890-7
ER  - 

@article{
author = "van Vliet, Danique and van Wegberg, Annemiek M. J. and Ahring, Kirsten and Bik-Multanowski, Miroslaw and Blau, Nenad and Bulut, Fatma D. and Casas, Kari and Didycz, Bozena and Đorđević, Maja and Federico, Antonio and Feillet, Francois and Gizewska, Maria and Gramer, Gwendolyn and Hertecant, Jozef L. and Hollak, Carla E. M. and Jorgensen, Jens V. and Karall, Daniela and Landau, Yuval and Leuzzi, Vincenzo and Mathisen, Per and Moseley, Kathryn and Mungan, Neslihan O. and Nardecchia, Francesca and Ounap, Katrin and Powell, Kimberly K. and Ramachandran, Radha and Rutsch, Frank and Setoodeh, Aria 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 = "2018",
abstract = "Background: Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. Methods: To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations  gt = 1200 mu mol/l; and 3) IQ  gt = 80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. Results: In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. Conclusions: Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re) present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.",
publisher = "BMC, London",
journal = "Orphanet Journal of Rare Diseases",
title = "Can untreated PKU patients escape from intellectual disability? A systematic review",
volume = "13",
doi = "10.1186/s13023-018-0890-7"
}

van Vliet, D., van Wegberg, A. M. J., Ahring, K., Bik-Multanowski, M., Blau, N., Bulut, F. D., Casas, K., Didycz, B., Đorđević, M., Federico, A., Feillet, F., Gizewska, M., Gramer, G., Hertecant, J. L., Hollak, C. E. M., Jorgensen, J. V., Karall, D., Landau, Y., Leuzzi, V., Mathisen, P., Moseley, K., Mungan, N. O., Nardecchia, F., Ounap, K., Powell, K. K., Ramachandran, R., Rutsch, F., Setoodeh, A., Stojiljković, M., Trefz, F. K., Usurelu, N., Wilson, C., van Karnebeek, C. D., Hanley, W. B.,& van Spronsen, F. J.. (2018). Can untreated PKU patients escape from intellectual disability? A systematic review. in Orphanet Journal of Rare Diseases
BMC, London., 13.
https://doi.org/10.1186/s13023-018-0890-7

van Vliet D, van Wegberg AMJ, Ahring K, Bik-Multanowski M, Blau N, Bulut FD, Casas K, Didycz B, Đorđević M, Federico A, Feillet F, Gizewska M, Gramer G, Hertecant JL, Hollak CEM, Jorgensen JV, Karall D, Landau Y, Leuzzi V, Mathisen P, Moseley K, Mungan NO, Nardecchia F, Ounap K, Powell KK, Ramachandran R, Rutsch F, Setoodeh A, Stojiljković M, Trefz FK, Usurelu N, Wilson C, van Karnebeek CD, Hanley WB, van Spronsen FJ. Can untreated PKU patients escape from intellectual disability? A systematic review. in Orphanet Journal of Rare Diseases. 2018;13.
doi:10.1186/s13023-018-0890-7 .

van Vliet, Danique, van Wegberg, Annemiek M. J., Ahring, Kirsten, Bik-Multanowski, Miroslaw, Blau, Nenad, Bulut, Fatma D., Casas, Kari, Didycz, Bozena, Đorđević, Maja, Federico, Antonio, Feillet, Francois, Gizewska, Maria, Gramer, Gwendolyn, Hertecant, Jozef L., Hollak, Carla E. M., Jorgensen, Jens V., Karall, Daniela, Landau, Yuval, Leuzzi, Vincenzo, Mathisen, Per, Moseley, Kathryn, Mungan, Neslihan O., Nardecchia, Francesca, Ounap, Katrin, Powell, Kimberly K., Ramachandran, Radha, Rutsch, Frank, Setoodeh, Aria, Stojiljković, Maja, Trefz, Fritz K., Usurelu, Natalia, Wilson, Callum, van Karnebeek, Clara D., Hanley, William B., van Spronsen, Francjan J., "Can untreated PKU patients escape from intellectual disability? A systematic review" in Orphanet Journal of Rare Diseases, 13 (2018),
https://doi.org/10.1186/s13023-018-0890-7 . .