{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:33:26Z","timestamp":1778103206861,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biomarin independent research grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: In 2011, a European phenylketonuria (PKU) survey reported that the blood phenylalanine (Phe) levels were well controlled in early life but deteriorated with age. Other studies have shown similar results across the globe. Different target blood Phe levels have been used throughout the years, and, in 2017, the European PKU guidelines defined new targets for blood Phe levels. This study aimed to evaluate blood Phe control in patients with PKU across Europe. Methods: nine centres managing PKU in Europe and Turkey participated. Data were collected retrospectively from medical and dietetic records between 2012 and 2018 on blood Phe levels, PKU severity, and medications. Results: A total of 1323 patients (age range:1\u201357, 51% male) participated. Patient numbers ranged from 59 to 320 in each centre. The most common phenotype was classical PKU (n = 625, 48%), followed by mild PKU (n = 357, 27%) and hyperphenylalaninemia (HPA) (n = 325, 25%). The mean percentage of blood Phe levels within the target range ranged from 65 \u00b1 54% to 88 \u00b1 49% for all centres. The percentage of Phe levels within the target range declined with increasing age (&lt;2 years: 89%; 2\u20135 years: 84%; 6\u201312 years: 73%; 13\u201318 years: 85%; 19\u201330 years: 64%; 31\u201340 years: 59%; and \u226541 years: 40%). The mean blood Phe levels were significantly lower and the percentage within the target range was significantly higher (p &lt; 0.001) in patients with HPA (290 \u00b1 325 \u03bcmol\/L; 96 \u00b1 24%) and mild PKU (365 \u00b1 224 \u03bcmol\/L; 77 \u00b1 36%) compared to classical PKU (458 \u00b1 350 \u03bcmol\/L, 54 \u00b1 46%). There was no difference between males and females in the mean blood Phe levels (p = 0.939), but the percentage of Phe levels within the target range was higher in females among school-age children (6\u201312 years; 83% in females vs. 78% in males; p = 0.005), adolescents (13\u201318 years; 62% in females vs. 59% in males; p = 0.034) and adults (31\u201340 years; 65% in females vs. 41% in males; p &lt; 0.001 and &gt;41 years; 43% in females vs. 28% in males; p &lt; 0.001). Patients treated with sapropterin (n = 222) had statistically significantly lower Phe levels compared to diet-only-treated patients (mean 391 \u00b1 334 \u03bcmol\/L; percentage within target 84 \u00b1 39% vs. 406 \u00b1 334 \u03bcmol\/L; 73 \u00b1 41%; p &lt; 0.001), although a blood Phe mean difference of 15 \u00b5mol\/L may not be clinically relevant. An increased frequency of blood Phe monitoring was associated with better metabolic control (p &lt; 0.05). The mean blood Phe (% Phe levels within target) from blood Phe samples collected weekly was 271 \u00b1 204 \u03bcmol\/L, (81 \u00b1 33%); for once every 2 weeks, it was 376 \u00b1 262 \u03bcmol\/L, (78 \u00b1 42%); for once every 4 weeks, it was 426 \u00b1 282 \u03bcmol\/L, (71 \u00b1 50%); and less than monthly samples, it was 534 \u00b1 468 \u03bcmol\/L, (70 \u00b1 58%). Conclusions: Overall, blood Phe control deteriorated with age. A higher frequency of blood sampling was associated with better blood Phe control with less variability. The severity of PKU and the available treatments and resources may impact the blood Phe control achieved by each treatment centre.<\/jats:p>","DOI":"10.3390\/nu16132064","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T06:51:53Z","timestamp":1719557513000},"page":"2064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Blood Phenylalanine Levels in Patients with Phenylketonuria from Europe between 2012 and 2018: Is It a Changing Landscape?"],"prefix":"10.3390","volume":"16","author":[{"given":"Alex","family":"Pinto","sequence":"first","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"},{"name":"School of Health Professions, Faculty of Health, University of Plymouth, Plymouth PL4 8AA, UK"}]},{"given":"Kirsten","family":"Ahring","sequence":"additional","affiliation":[{"name":"Departments of Paediatrics and Clinical Genetics, PKU Clinic, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-1314","authenticated-orcid":false,"given":"Manuela Ferreira","family":"Almeida","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, E.P.E. (ULSSA), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00e1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, E.P.E. (ULSSA), 4099-001 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto-UMIB\/ICBAS\/UP, 4050-313 Porto, Portugal"}]},{"given":"Catherine","family":"Ashmore","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-8956","authenticated-orcid":false,"given":"Amaya","family":"B\u00e9langer-Quintana","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Metab\u00f3licas Cong\u00e9nitas, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-137X","authenticated-orcid":false,"given":"Alberto","family":"Burlina","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, Department of Women\u2019s and Children\u2019s Health, University Hospital, 35128 Padova, Italy"}]},{"given":"Turgay","family":"Co\u015fkun","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Gevher Nesibe Cd., 06230 Ankara, Turkey"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8699","authenticated-orcid":false,"given":"Anne","family":"Daly","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"given":"Esther","family":"van Dam","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases, Beatrix Children\u2019s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}]},{"given":"Ali","family":"Dursun","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Gevher Nesibe Cd., 06230 Ankara, Turkey"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7654-3621","authenticated-orcid":false,"given":"Sharon","family":"Evans","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"given":"Fran\u00e7ois","family":"Feillet","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Reference Center for Inborn Errors of Metabolism, H\u00f4pital d\u2019Enfants Brabois, CHU Nancy, 54500 Vandoeuvre les Nancy, France"}]},{"given":"Maria","family":"Gi\u017cewska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland"}]},{"given":"Hulya","family":"G\u00f6kmen-\u00d6zel","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-0095","authenticated-orcid":false,"given":"Mary","family":"Hickson","sequence":"additional","affiliation":[{"name":"School of Health Professions, Faculty of Health, University of Plymouth, Plymouth PL4 8AA, UK"}]},{"given":"Yteke","family":"Hoekstra","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases, Beatrix Children\u2019s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}]},{"given":"Fatma","family":"Ilgaz","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey"}]},{"given":"Richard","family":"Jackson","sequence":"additional","affiliation":[{"name":"Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool L69 3GL, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0760-5120","authenticated-orcid":false,"given":"Alicja","family":"Le\u015bniak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland"}]},{"given":"Christian","family":"Loro","sequence":"additional","affiliation":[{"name":"Division of Inherited Metabolic Diseases, Reference Centre Expanded Newborn Screening, Department of Women\u2019s and Children\u2019s Health, University Hospital, 35128 Padova, Italy"}]},{"given":"Katarzyna","family":"Malicka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5981-6456","authenticated-orcid":false,"given":"Micha\u0142","family":"Patalan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School (NMS), Faculdade de Ci\u00eancias M\u00e9dicas, (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o em Tecnologias e Servi\u00e7os de Sa\u00fade (CINTESIS), NOVA Medical School (NMS), Faculdade de Ci\u00eancias M\u00e9dicas, (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Reference Centre of Inherited Metabolic Diseases, Unidade Local de Sa\u00fade, 1169-045 Lisboa, Portugal"},{"name":"Comprehensive Health Research Centre (CHRC), NOVA Medical School, (NMS), Faculdade de Ci\u00eancias M\u00e9dicas (FCM), Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Serap","family":"Sivri","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Gevher Nesibe Cd., 06230 Ankara, Turkey"}]},{"given":"Iris","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases, Beatrix Children\u2019s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-1929","authenticated-orcid":false,"given":"Francjan","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases, Beatrix Children\u2019s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}]},{"given":"Kamilla","family":"Str\u0105czek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology, Pomeranian Medical University, 70-204 Szczecin, Poland"}]},{"given":"Ay\u015feg\u00fcl","family":"Tokatli","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Gevher Nesibe Cd., 06230 Ankara, Turkey"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ajhg.2020.06.006","article-title":"The Genetic Landscape and Epidemiology of Phenylketonuria","volume":"107","author":"Hillert","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41572-021-00267-0","article-title":"Phenylketonuria","volume":"7","author":"Blau","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100032","DOI":"10.1016\/j.nbas.2022.100032","article-title":"Brain and cognitive ageing: The present, and some predictions (\u2026about the future)","volume":"2","author":"Cox","year":"2022","journal-title":"Aging Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"107583","DOI":"10.1016\/j.ymgme.2023.107583","article-title":"Phenylketonuria and the brain","volume":"139","author":"Rovelli","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107666","DOI":"10.1016\/j.ymgme.2023.107666","article-title":"Towards precision medicine for phenylketonuria: The effect of restoring a strict metabolic control in adult patients with early-treated phenylketonuria","volume":"140","author":"Manti","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Romani, C., Olson, A., Aitkenhead, L., Baker, L., Patel, D., Spronsen, F.V., MacDonald, A., Wegberg, A.V., and Huijbregts, S. (2022). Meta-analyses of cognitive functions in early-treated adults with phenylketonuria. Neurosci. Biobehav. Rev., 143.","DOI":"10.1016\/j.neubiorev.2022.104925"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"113526","DOI":"10.1016\/j.jpeds.2023.113526","article-title":"Neuropsychiatric Function Improvement in Pediatric Patients with Phenylketonuria","volume":"260","author":"Grant","year":"2023","journal-title":"J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1186\/s13023-021-02138-z","article-title":"Mental health diagnoses in adults with phenylketonuria: A retrospective systematic audit in a large UK single centre","volume":"16","author":"Altman","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2017.03.002","article-title":"Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study","volume":"121","author":"Bilder","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00415-019-09608-2","article-title":"Neurological manifestations in adults with phenylketonuria: New cases and review of the literature","volume":"267","author":"Jaulent","year":"2020","journal-title":"J. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106969","DOI":"10.1016\/j.ymgme.2022.106969","article-title":"The impact of metabolic control on cognition, neurophysiology, and well-being in PKU: A systematic review and meta-analysis of the within-participant literature","volume":"138","author":"Thomas","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s13023-019-1153-y","article-title":"Clinical burden of illness in patients with phenylketonuria (PKU) and associated comorbidities\u2014A retrospective study of German health insurance claims data","volume":"14","author":"Trefz","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ymgme.2019.12.007","article-title":"5-year retrospective analysis of patients with phenylketonuria (PKU) and hyperphenylalaninemia treated at two specialized clinics","volume":"129","author":"Levy","year":"2020","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1186\/s13023-022-02488-2","article-title":"Expert opinion of an Italian working group on the assessment of cognitive, psychological, and neurological outcomes in pediatric, adolescent, and adult patients with phenylketonuria","volume":"17","author":"Manti","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107625","DOI":"10.1016\/j.ymgme.2023.107625","article-title":"Health status and comorbidities of adult patients with phenylketonuria (PKU) in France with a focus on early-diagnosed patients\u2014A nationwide study of health insurance claims data","volume":"139","author":"Maillot","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100358","DOI":"10.1016\/j.gim.2022.12.005","article-title":"Phenylalanine hydroxylase deficiency treatment and management: A systematic evidence review of the American College of Medical Genetics and Genomics (ACMG)","volume":"25","author":"Adams","year":"2023","journal-title":"Genet. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/ped.14399","article-title":"Guide for diagnosis and treatment of hyperphenylalaninemia","volume":"63","author":"Shintaku","year":"2021","journal-title":"Pediatr. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The complete European guidelines on phenylketonuria: Diagnosis and treatment","volume":"12","author":"MacDonald","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/gim.2013.157","article-title":"Phenylalanine hydroxylase deficiency: Diagnosis and management guideline","volume":"16","author":"Vockley","year":"2014","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13023-020-01391-y","article-title":"PKU dietary handbook to accompany PKU guidelines","volume":"15","author":"MacDonald","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-015-0378-7","article-title":"Special low protein foods for phenylketonuria: Availability in Europe and an examination of their nutritional profile","volume":"10","author":"Pena","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2019.04.004","article-title":"International best practice for the evaluation of responsiveness to sapropterin dihydrochloride in patients with phenylketonuria","volume":"127","author":"Muntau","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.ymgme.2015.02.003","article-title":"Long-term safety and efficacy of sapropterin: The PKUDOS registry experience","volume":"114","author":"Longo","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108114","DOI":"10.1016\/j.ymgme.2023.108114","article-title":"Long-term comparative effectiveness of pegvaliase versus medical nutrition therapy with and without sapropterin in adults with phenylketonuria","volume":"141","author":"Burton","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13023-015-0227-8","article-title":"Long-term follow-up of patients with phenylketonuria treated with tetrahydrobiopterin: A seven years experience","volume":"10","author":"Scala","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108122","DOI":"10.1016\/j.ymgme.2023.108122","article-title":"Evaluating change in diet with pegvaliase treatment in adults with phenylketonuria: Analysis of phase 3 clinical trial data","volume":"141","author":"Rohr","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"107697","DOI":"10.1016\/j.ymgme.2023.107697","article-title":"Two-year interim safety and efficacy of pegvaliase in Japanese adults with phenylketonuria","volume":"140","author":"Ishige","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107564","DOI":"10.1016\/j.ymgme.2023.107564","article-title":"Two years of pegvaliase in Germany: Experiences and best practice recommendations","volume":"139","author":"Baerwald","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107737","DOI":"10.1016\/j.ymgme.2023.107737","article-title":"Best practice recommendations for the management of anxiety during the pegvaliase journey","volume":"141","author":"Bjoraker","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0140-6736(02)09334-0","article-title":"How practical are recommendations for dietary control in phenylketonuria?","volume":"360","author":"Walter","year":"2002","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ymgme.2017.01.001","article-title":"Adherence to clinic recommendations among patients with phenylketonuria in the United States","volume":"120","author":"Jurecki","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ejcn.2010.258","article-title":"Blood phenylalanine control in phenylketonuria: A survey of 10 European centres","volume":"65","author":"Ahring","year":"2011","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kanufre, V., Almeida, M.F., Barbosa, C.S., Carmona, C., Bandeira, A., Martins, E., Rocha, S., Guimas, A., Ribeiro, R., and MacDonald, A. (2021). Metabolic Control of Patients with Phenylketonuria in a Portuguese Metabolic Centre Comparing Three Different Recommendations. Nutrients, 13.","DOI":"10.3390\/nu13093118"},{"key":"ref_34","unstructured":"Blau, N. (2024, June 19). BIOPKU. Available online: http:\/\/www.biopku.org\/home\/home.asp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(10)60961-0","article-title":"Phenylketonuria","volume":"376","author":"Blau","year":"2010","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1515\/IJAMH.2004.16.1.41","article-title":"Blood phenylalanine control in adolescents with phenylketonuria","volume":"16","author":"Walter","year":"2004","journal-title":"Int. J. Adolesc. Med. Health"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100897","DOI":"10.1016\/j.ymgmr.2022.100897","article-title":"A retrospective analysis of metabolic control in children with PKU in the COVID-19 era","volume":"32","author":"Becsei","year":"2022","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Walkowiak, D., Miko\u0142u\u0107, B., Mozrzymas, R., Ka\u0142u\u017cny, \u0141., Didycz, B., Jaglowska, J., Kurylak, D., and Walkowiak, J. (2021). The Impact of the First 2020 COVID-19 Lockdown on the Metabolic Control of Patients with Phenylketonuria. Nutrients, 13.","DOI":"10.3390\/nu13062024"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"107684","DOI":"10.1016\/j.ymgme.2023.107684","article-title":"Metabolic control and clinical outcome in adolescents with phenylketonuria","volume":"140","author":"Nardecchia","year":"2023","journal-title":"Mol. Genet. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ymgme.2021.11.003","article-title":"The increasing importance of LNAA supplementation in phenylketonuria at higher plasma phenylalanine concentrations","volume":"135","author":"Kema","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ymgmr.2018.06.007","article-title":"Living with phenylketonuria in adulthood: The PKU ATTITUDE study","volume":"16","author":"Cazzorla","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ilgaz, F., Ford, S., O\u2018Driscoll, M.F., and MacDonald, A. (2023). Adult PKU Clinics in the UK-Users\u2019 Experiences and Perspectives. Nutrients, 15.","DOI":"10.3390\/nu15204352"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.ajcnut.2024.01.023","article-title":"Phenylketonuria in adults: What do we know?","volume":"119","author":"Lachmann","year":"2024","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ymgmr.2018.10.002","article-title":"Living with Phenylketonuria: Lessons from the PKU community","volume":"17","author":"Ford","year":"2018","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100571","DOI":"10.1016\/j.ymgmr.2020.100571","article-title":"Strategies to engage lost to follow-up patients with phenylketonuria in the United States: Best practice recommendations","volume":"23","author":"Beazer","year":"2020","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/jimd.12413","article-title":"Long-term cognitive and psychosocial outcomes in adults with phenylketonuria","volume":"44","author":"Aitkenhead","year":"2021","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1186\/s13023-021-02086-8","article-title":"Italian national consensus statement on management and pharmacological treatment of phenylketonuria","volume":"16","author":"Burlina","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Robertson, L., Adam, S., Ellerton, C., Ford, S., Hill, M., Randles, G., Woodall, A., Young, C., and MacDonald, A. (2022). Dietetic Management of Adults with Phenylketonuria (PKU) in the UK: A Care Consensus Document. Nutrients, 14.","DOI":"10.3390\/nu14030576"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1186\/s13023-019-1225-z","article-title":"Adult cognitive outcomes in phenylketonuria: Explaining causes of variability beyond average Phe levels","volume":"14","author":"Romani","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ymgme.2014.01.012","article-title":"Variability in phenylalanine control predicts IQ and executive abilities in children with phenylketonuria","volume":"111","author":"Hood","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13023-016-0410-6","article-title":"Ten years of specialized adult care for phenylketonuria\u2014A single-centre experience","volume":"11","author":"Thiele","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Peres, M., Almeida, M.F., Pinto, \u00c9.J., Carmona, C., Rocha, S., Guimas, A., Ribeiro, R., Martins, E., Bandeira, A., and MacDonald, A. (2021). Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results After Two Years of Follow-Up with an Adult Team. Nutrients, 13.","DOI":"10.3390\/nu13030799"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s10545-005-4478-8","article-title":"Living with phenylketonuria: Perspectives of patients and their families","volume":"28","author":"Bilginsoy","year":"2005","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108361","DOI":"10.1016\/j.ymgme.2024.108361","article-title":"Satisfaction with home blood sampling methods and expectations for future point-of-care testing in phenylketonuria: Perspectives from patients and professionals","volume":"142","author":"Kuypers","year":"2024","journal-title":"Mol. Genet. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/jmd2.12398","article-title":"Investigation of the relationship between phenylalanine in venous plasma and capillary blood using volumetric blood collection devices","volume":"64","author":"Carling","year":"2023","journal-title":"JIMD Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13023-020-1343-7","article-title":"Dried blood spot versus venous blood sampling for phenylalanine and tyrosine","volume":"15","author":"Koehorst","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1136\/adc.78.2.122","article-title":"Does a single plasma phenylalanine predict quality of control in phenylketonuria?","volume":"78","author":"MacDonald","year":"1998","journal-title":"Arch. Dis. 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