TY  - JOUR
AU  - Hillert, Alicia
AU  - Anikster, Yair
AU  - Belanger-Quintana, Amaya
AU  - Burlina, Alberto
AU  - Burton, Barbara K.
AU  - Carducci, Carla
AU  - Chiesa, Ana E.
AU  - Christodoulou, John
AU  - Đorđević, Maja
AU  - Desviat, Lourdes R.
AU  - Eliyahu, Aviva
AU  - Evers, Roeland A. F.
AU  - Fajkusova, Lena
AU  - Feillet, Francois
AU  - Bonfim-Freitas, Pedro E.
AU  - Gizewska, Maria
AU  - Gundorova, Polina
AU  - Karall, Daniela
AU  - Kneller, Katya
AU  - Kutsev, Sergey, I
AU  - Leuzzi, Vincenzo
AU  - Levy, Harvey L.
AU  - Lichter-Konecki, Uta
AU  - Muntau, Ania C.
AU  - Namour, Fares
AU  - Oltarzewski, Mariusz
AU  - Paras, Andrea
AU  - Perez, Belen
AU  - Polak, Emil
AU  - Polyakov, Alexander, V
AU  - Porta, Francesco
AU  - Rohrbach, Marianne
AU  - Scholl-Burgi, Sabine
AU  - Specola, Norma
AU  - Stojiljković, Maja
AU  - Shen, Nan
AU  - Santana-da Silva, Luiz C.
AU  - Skouma, Anastasia
AU  - van Spronsen, Francjan
AU  - Stoppioni, Vera
AU  - Thony, Beat
AU  - Trefz, Friedrich K.
AU  - Vockley, Jerry
AU  - Yu, Youngguo
AU  - Zschocke, Johannes
AU  - Hoffmann, Georg F.
AU  - Garbade, Sven F.
AU  - Blau, Nenad
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1314
AB  - Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A gt G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C gt T (p.Arg408Trp) (22.2%), c.1066-11G gt A (IVS10-11G gt A) (6.4%), and c.782G gt A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G gt A];[1066-11G gt A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.
PB  - Cell Press, Cambridge
T2  - American Journal of Human Genetics
T1  - The Genetic Landscape and Epidemiology of Phenylketonuria
EP  - 250
IS  - 2
SP  - 234
VL  - 107
DO  - 10.1016/j.ajhg.2020.06.006
ER  - 

@article{
author = "Hillert, Alicia and Anikster, Yair and Belanger-Quintana, Amaya and Burlina, Alberto and Burton, Barbara K. and Carducci, Carla and Chiesa, Ana E. and Christodoulou, John and Đorđević, Maja and Desviat, Lourdes R. and Eliyahu, Aviva and Evers, Roeland A. F. and Fajkusova, Lena and Feillet, Francois and Bonfim-Freitas, Pedro E. and Gizewska, Maria and Gundorova, Polina and Karall, Daniela and Kneller, Katya and Kutsev, Sergey, I and Leuzzi, Vincenzo and Levy, Harvey L. and Lichter-Konecki, Uta and Muntau, Ania C. and Namour, Fares and Oltarzewski, Mariusz and Paras, Andrea and Perez, Belen and Polak, Emil and Polyakov, Alexander, V and Porta, Francesco and Rohrbach, Marianne and Scholl-Burgi, Sabine and Specola, Norma and Stojiljković, Maja and Shen, Nan and Santana-da Silva, Luiz C. and Skouma, Anastasia and van Spronsen, Francjan and Stoppioni, Vera and Thony, Beat and Trefz, Friedrich K. and Vockley, Jerry and Yu, Youngguo and Zschocke, Johannes and Hoffmann, Georg F. and Garbade, Sven F. and Blau, Nenad",
year = "2020",
abstract = "Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A gt G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C gt T (p.Arg408Trp) (22.2%), c.1066-11G gt A (IVS10-11G gt A) (6.4%), and c.782G gt A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G gt A];[1066-11G gt A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.",
publisher = "Cell Press, Cambridge",
journal = "American Journal of Human Genetics",
title = "The Genetic Landscape and Epidemiology of Phenylketonuria",
pages = "250-234",
number = "2",
volume = "107",
doi = "10.1016/j.ajhg.2020.06.006"
}

Hillert, A., Anikster, Y., Belanger-Quintana, A., Burlina, A., Burton, B. K., Carducci, C., Chiesa, A. E., Christodoulou, J., Đorđević, M., Desviat, L. R., Eliyahu, A., Evers, R. A. F., Fajkusova, L., Feillet, F., Bonfim-Freitas, P. E., Gizewska, M., Gundorova, P., Karall, D., Kneller, K., Kutsev, S. I., Leuzzi, V., Levy, H. L., Lichter-Konecki, U., Muntau, A. C., Namour, F., Oltarzewski, M., Paras, A., Perez, B., Polak, E., Polyakov, A. V., Porta, F., Rohrbach, M., Scholl-Burgi, S., Specola, N., Stojiljković, M., Shen, N., Santana-da Silva, L. C., Skouma, A., van Spronsen, F., Stoppioni, V., Thony, B., Trefz, F. K., Vockley, J., Yu, Y., Zschocke, J., Hoffmann, G. F., Garbade, S. F.,& Blau, N.. (2020). The Genetic Landscape and Epidemiology of Phenylketonuria. in American Journal of Human Genetics
Cell Press, Cambridge., 107(2), 234-250.
https://doi.org/10.1016/j.ajhg.2020.06.006

Hillert A, Anikster Y, Belanger-Quintana A, Burlina A, Burton BK, Carducci C, Chiesa AE, Christodoulou J, Đorđević M, Desviat LR, Eliyahu A, Evers RAF, Fajkusova L, Feillet F, Bonfim-Freitas PE, Gizewska M, Gundorova P, Karall D, Kneller K, Kutsev SI, Leuzzi V, Levy HL, Lichter-Konecki U, Muntau AC, Namour F, Oltarzewski M, Paras A, Perez B, Polak E, Polyakov AV, Porta F, Rohrbach M, Scholl-Burgi S, Specola N, Stojiljković M, Shen N, Santana-da Silva LC, Skouma A, van Spronsen F, Stoppioni V, Thony B, Trefz FK, Vockley J, Yu Y, Zschocke J, Hoffmann GF, Garbade SF, Blau N. The Genetic Landscape and Epidemiology of Phenylketonuria. in American Journal of Human Genetics. 2020;107(2):234-250.
doi:10.1016/j.ajhg.2020.06.006 .

Hillert, Alicia, Anikster, Yair, Belanger-Quintana, Amaya, Burlina, Alberto, Burton, Barbara K., Carducci, Carla, Chiesa, Ana E., Christodoulou, John, Đorđević, Maja, Desviat, Lourdes R., Eliyahu, Aviva, Evers, Roeland A. F., Fajkusova, Lena, Feillet, Francois, Bonfim-Freitas, Pedro E., Gizewska, Maria, Gundorova, Polina, Karall, Daniela, Kneller, Katya, Kutsev, Sergey, I, Leuzzi, Vincenzo, Levy, Harvey L., Lichter-Konecki, Uta, Muntau, Ania C., Namour, Fares, Oltarzewski, Mariusz, Paras, Andrea, Perez, Belen, Polak, Emil, Polyakov, Alexander, V, Porta, Francesco, Rohrbach, Marianne, Scholl-Burgi, Sabine, Specola, Norma, Stojiljković, Maja, Shen, Nan, Santana-da Silva, Luiz C., Skouma, Anastasia, van Spronsen, Francjan, Stoppioni, Vera, Thony, Beat, Trefz, Friedrich K., Vockley, Jerry, Yu, Youngguo, Zschocke, Johannes, Hoffmann, Georg F., Garbade, Sven F., Blau, Nenad, "The Genetic Landscape and Epidemiology of Phenylketonuria" in American Journal of Human Genetics, 107, no. 2 (2020):234-250,
https://doi.org/10.1016/j.ajhg.2020.06.006 . .

TY  - 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 . .

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 . .