{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T23:37:12Z","timestamp":1775173032566,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Blood phenylalanine (Phe) is used as the primary marker to evaluate metabolic control. Our study aimed to describe the metabolic control of patients with phenylketonuria (PKU) comparing three different treatment recommendations (European guidelines\/US guidelines\/Portuguese consensus). This was a retrospective, observational, single centre study in patients with PKU collecting data on blood Phe levels from 2017. Nutritional intake data and sapropterin (BH4) prescription were collected at the last appointment of 2017. The final sample studied included 87 patients (48% females) [13 hyperphenylalaninemia; 47 mild PKU; 27 classical PKU] with a median age of 18 y (range: 1\u201336 y). The median number of blood Phe measurements for patients was 21 (range: 6\u201389). In patients aged &lt; 12 y, the median blood Phe level was 300 \u03bcmol\/L (range 168\u2013480) and 474 \u03bcmol\/L (range 156\u20131194) for patients \u2265 12 y. Overall, a median of 83% of blood Phe levels were within the European PKU guidelines target range. In patients aged \u2265 12 years, there was a higher median % of blood Phe levels within the European PKU guidelines target range (\u226512 y: 84% vs. &lt;12 y: 56%). In children &lt; 12 y with classical PKU (n = 2), only 34% of blood Phe levels were within target range for all 3 guidelines and 49% with mild PKU (n = 11). Girls had better control than boys (89% vs. 66% median Phe levels within European Guidelines). Although it is clear that 50% or more patients were unable to achieve acceptable metabolic control on current treatment options, a globally agreed upper Phe target associated with optimal outcomes for age groups is necessary. More studies need to examine how clinics with dissimilar resources, different therapeutic Phe targets and frequency of monitoring relate to metabolic control.<\/jats:p>","DOI":"10.3390\/nu13093118","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T21:47:38Z","timestamp":1630964858000},"page":"3118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Metabolic Control of Patients with Phenylketonuria in a Portuguese Metabolic Centre Comparing Three Different Recommendations"],"prefix":"10.3390","volume":"13","author":[{"given":"Viviane","family":"Kanufre","sequence":"first","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"},{"name":"N\u00facleo de A\u00e7\u00f5es e Pesquisa em Apoio Diagn\u00f3stico (NUPAD), School of Medicine, Federal University of Minas Gerais (UFMG), Avenida Professor Alfredo Balena, 190, Belo Horizonte 30130-100, Brazil"},{"name":"Hospital das Cl\u00ednicas, UFMG, Avenida Professor Alfredo Balena, 110, Santa Efig\u00eania, Belo Horizonte 30130-100, Brazil"}]},{"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, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 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":"Catarina Sousa","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"}]},{"given":"Carla","family":"Carmona","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 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":"Anabela","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"}]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 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":"Sara","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"}]},{"given":"Arlindo","family":"Guimas","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"}]},{"given":"Rosa","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"given":"Alex","family":"Pinto","sequence":"additional","affiliation":[{"name":"Birmingham Women\u2019s and Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica, Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia na \u00c1rea de Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio do Porto-CHUPorto, 4099-001 Porto, Portugal"},{"name":"Nutrition & Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Campo M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisbon, Portugal"},{"name":"Centre for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/8904_2017_60","article-title":"The Use of d2 and Benton Tests for Assessment of Attention Deficits and Visual Memory in Teenagers with Phenylketonuria","volume":"40","author":"Didycz","year":"2018","journal-title":"JIMD Rep."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.ymgme.2011.08.023","article-title":"Nutrition in phenylketonuria","volume":"104","author":"MacDonald","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ejcn.2016.54","article-title":"Protein substitutes for phenylketonuria in Europe: Access and nutritional composition","volume":"70","author":"Pena","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13023-019-1011-y","article-title":"Glycomacropeptide: Long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU","volume":"14","author":"Daly","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13023-021-01721-8","article-title":"Continuous use of glycomacropeptide in the nutritional management of patients with phenylketonuria: A clinical perspective","volume":"16","author":"Pena","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/ejcn.2017.38","article-title":"Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source","volume":"71","author":"Pinto","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_10","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_11","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_12","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_13","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/s41436-018-0403-z","article-title":"Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria","volume":"21","author":"Longo","year":"2019","journal-title":"Genet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF02312549","article-title":"Diet termination in children with phenylketonuria: A review of psychological assessments used to determine outcome","volume":"3","author":"Waisbren","year":"1980","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ymgme.2007.05.006","article-title":"Phenylalanine blood levels and clinical outcomes in phenylketonuria: A systematic literature review and meta-analysis","volume":"92","author":"Waisbren","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1037\/neu0000337","article-title":"Cognitive outcomes in early-treated adults with phenylketonuria (PKU): A comprehensive picture across domains","volume":"31","author":"Palermo","year":"2017","journal-title":"Neuropsychology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1037\/neu0000358","article-title":"Cognitive profile and mental health in adult phenylketonuria: A PKU-COBESO study","volume":"31","author":"Jahja","year":"2017","journal-title":"Neuropsychology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1023\/A:1020158631102","article-title":"Phenylketonuria in adulthood: A collaborative study","volume":"25","author":"Koch","year":"2002","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1037\/neu0000336","article-title":"The impact of phenylalanine levels on cognitive outcomes in adults with phenylketonuria: Effects across tasks and developmental stages","volume":"31","author":"Romani","year":"2017","journal-title":"Neuropsychology"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S2213-8587(17)30201-2","article-title":"Issues with European guidelines for phenylketonuria","volume":"5","author":"Burgard","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_22","first-page":"44","article-title":"Consenso para o tratamento nutricional de fenilceton\u00faria (Article in Portuguese)","volume":"38","author":"Rocha","year":"2007","journal-title":"Acta Pediatr. Port."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1515\/jpem-2018-0527","article-title":"The European Phenylketonuria Guidelines and the challenges on management practices in Portugal","volume":"32","author":"Sousa","year":"2019","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_24","unstructured":"Joint WHO\/FAO\/UNU Expert Consultation (2007). Protein and Amino Acid Requirements in Human Nutrition, World Health Organization."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kraleva, D., Evans, S., Pinto, A., Daly, A., Ashmore, C., Pointon-Bell, K., Rocha, J.C., and MacDonald, A. (2020). Protein Labelling Accuracy for UK Patients with PKU Following a Low Protein Diet. Nutrients, 12.","DOI":"10.3390\/nu12113440"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Newbould, E., Pinto, A., Evans, S., Ford, S., O\u2019Driscoll, M., Ashmore, C., Daly, A., and MacDonald, A. (2021). Accidental Consumption of Aspartame in Phenylketonuria: Patient Experiences. Nutrients, 13.","DOI":"10.3390\/nu13020707"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1016\/j.ymgme.2013.08.013","article-title":"Neurocognitive functioning in adults with phenylketonuria: Results of a long term study","volume":"110","author":"Weglage","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e399","DOI":"10.1212\/WNL.0000000000011088","article-title":"Phenylalanine Effects on Brain Function in Adult Phenylketonuria","volume":"96","author":"Pilotto","year":"2021","journal-title":"Neurology"},{"key":"ref_29","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_30","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."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/9\/3118\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:57:11Z","timestamp":1760165831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/9\/3118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,6]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["nu13093118"],"URL":"https:\/\/doi.org\/10.3390\/nu13093118","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,6]]}}}