{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:00:37Z","timestamp":1770271237841,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Portuguese Society of Metabolic Diseases (SPDM)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: In phenylketonuria (PKU) changes in dietary patterns and behaviors in sapropterin-responsive populations have not been widely reported. We aimed to assess changes in food quality, mental health and burden of care in a paediatric PKU sapropterin-responsive cohort. Methods: In an observational, longitudinal study, patient questionnaires on food frequency, neophobia, anxiety and depression, impact on family and burden of care were applied at baseline, 3 and 6-months post successful sapropterin-responsiveness testing (defined as a 30% reduction in blood phenylalanine levels). Results: 17 children (10.8 \u00b1 4.2 years) completed 6-months follow-up. Patients body mass index (BMI) z-scores remained unchanged after sapropterin initiation. Blood phenylalanine was stable. Natural protein increased (p &lt; 0.001) and protein substitute intake decreased (p = 0.002). There were increases in regular cow\u2019s milk (p = 0.001), meat\/fish, eggs (p = 0.005), bread (p = 0.01) and pasta (p = 0.011) intakes but special low-protein foods intake decreased. Anxiety (p = 0.016) and depression (p = 0.022) decreased in caregivers. The impact-on-family, familial-social impact (p = 0.002) and personal strain (p = 0.001) lessened. After sapropterin, caregivers spent less time on PKU tasks, the majority ate meals outside the home more regularly and fewer caregivers had to deny food choices to their children. Conclusion: There were significant positive changes in food patterns, behaviors and burden of care in children with PKU and their families after 6-months on sapropterin treatment.<\/jats:p>","DOI":"10.3390\/nu15163603","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T10:42:29Z","timestamp":1692268949000},"page":"3603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact on Diet Quality and Burden of Care in Sapropterin Dihydrochloride Use in Children with Phenylketonuria: A 6 Month Follow-Up Report"],"prefix":"10.3390","volume":"15","author":[{"given":"Maria In\u00eas","family":"Gama","sequence":"first","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"},{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas da Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8699","authenticated-orcid":false,"given":"Anne","family":"Daly","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"given":"Catherine","family":"Ashmore","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"given":"Sharon","family":"Evans","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-1839","authenticated-orcid":false,"given":"Andr\u00e9","family":"Moreira-Ros\u00e1rio","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas da Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"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, Faculdade de Ci\u00eancias M\u00e9dicas da Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS@RISE, Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universit\u00e1rio de Lisboa Central, 1169-045 Lisboa, Portugal"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1517\/17425255.2013.804064","article-title":"Sapropterin dihydrochloride for the treatment of hyperphenylalaninemias","volume":"9","author":"Blau","year":"2013","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_3","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_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ymgmr.2015.12.004","article-title":"Phenylketonuria (PKU): A problem solved?","volume":"6","author":"Brown","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Green, B., Browne, R., Firman, S., Hill, M., Rahman, Y., Kaalund Hansen, K., Adam, S., Skeath, R., Hallam, P., and Herlihy, I. (2019). Nutritional and Metabolic Characteristics of UK Adult Phenylketonuria Patients with Varying Dietary Adherence. Nutrients, 11.","DOI":"10.3390\/nu11102459"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13023-018-0847-x","article-title":"Carbohydrate status in patients with phenylketonuria","volume":"13","author":"Couce","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13023-019-1188-0","article-title":"The cardiovascular phenotype of adult patients with phenylketonuria","volume":"14","author":"Azabdaftari","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13023-016-0508-x","article-title":"Lipid profile status and other related factors in patients with Hyperphenylalaninaemia","volume":"11","author":"Couce","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1017\/S0954422418000173","article-title":"Optimising amino acid absorption: Essential to improve nitrogen balance and metabolic control in phenylketonuria","volume":"32","author":"MacDonald","year":"2019","journal-title":"Nutr. Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/8904_2017_23","article-title":"Treatment Adherence and Psychological Wellbeing in Maternal Carers of Children with Phenylketonuria (PKU)","volume":"37","author":"Medford","year":"2017","journal-title":"JIMD Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"350","DOI":"10.17712\/nsj.2015.4.20150319","article-title":"Depression and anxiety among parents of phenylketonuria children","volume":"20","author":"Gunduz","year":"2015","journal-title":"Neurosciences"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shaji Thomas, D., KY, D., and Arulappan, J. (2021). Health Related Quality of Life of Caregivers of Children and Adolescents with Phenylketonuria: A Systematic Review. Glob. Pediatr. Health, 8.","DOI":"10.1177\/2333794X211065333"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100823","DOI":"10.1016\/j.ymgmr.2021.100823","article-title":"Quality of life in children living with PKU\u2014A single-center, cross-sectional, observational study from Hungary","volume":"29","author":"Becsei","year":"2021","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_16","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_17","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_18","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1016\/j.ymgme.2005.05.014","article-title":"Clinical and nutritional evaluation of phenylketonuric patients on tetrahydrobiopterin monotherapy","volume":"86","author":"Lambruschini","year":"2005","journal-title":"Mol. Genet. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s10545-010-9224-1","article-title":"BH(4) therapy impacts the nutrition status and intake in children with phenylketonuria: 2-year follow-up","volume":"33","author":"Singh","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/s13023-021-01968-1","article-title":"Long-term efficacy and safety of sapropterin in patients who initiated sapropterin at <\u20094 years of age with phenylketonuria: Results of the 3-year extension of the SPARK open-label, multicentre, randomised phase IIIb trial","volume":"16","author":"Muntau","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Evers, R.A.F., van Wegberg, A.M.J., MacDonald, A., Huijbregts, S.C.J., Leuzzi, V., and van Spronsen, F.J. (2022). Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients: Does It Improve Outcomes?. Nutrients, 14.","DOI":"10.3390\/nu14183874"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/8904_2012_176","article-title":"Nutritional Changes and Micronutrient Supply in Patients with Phenylketonuria Under Therapy with Tetrahydrobiopterin (BH(4))","volume":"9","author":"Thiele","year":"2013","journal-title":"JIMD Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ymgmr.2015.07.002","article-title":"The challenge of long-term tetrahydrobiopterin (BH4) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply","volume":"4","author":"Thiele","year":"2015","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ilgaz, F., Marsaux, C., Pinto, A., Singh, R., Rohde, C., Karabulut, E., G\u00f6kmen-\u00d6zel, H., Kuhn, M., and MacDonald, A. (2021). Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13031040"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rodrigues, C., Pinto, A., Faria, A., Teixeira, D., van Wegberg, A.M.J., Ahring, K., Feillet, F., Calhau, C., MacDonald, A., and Moreira-Ros\u00e1rio, A. (2021). Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13103443"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Evans, S., Ashmore, C., Daly, A., Jackson, R., Pinto, A., and MacDonald, A. (2022). Validation of a Low-protein Semi-Quantitative Food Frequency Questionnaire. Nutrients, 14.","DOI":"10.3390\/nu14081595"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/jhn.12346","article-title":"Food acceptance and neophobia in children with phenylketonuria: A prospective controlled study","volume":"29","author":"Evans","year":"2016","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","article-title":"The hospital anxiety and depression scale","volume":"67","author":"Zigmond","year":"1983","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/00005650-198004000-00010","article-title":"The development of an impact-on-family scale: Preliminary findings","volume":"18","author":"Stein","year":"1980","journal-title":"Med. Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"660","DOI":"10.2471\/BLT.07.043497","article-title":"Development of a WHO growth reference for school-aged children and adolescents","volume":"85","author":"Onyango","year":"2007","journal-title":"Bull. World Health Organ."},{"key":"ref_32","unstructured":"(2023, January 20). BIOPKU. Available online: http:\/\/www.biopku.org\/home\/home.asp."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wood, G., Evans, S., Pointon-Bell, K., Rocha, J.C., and MacDonald, A. (2020). Special Low Protein Foods in the UK: An Examination of Their Macronutrient Composition in Comparison to Regular Foods. Nutrients, 12.","DOI":"10.3390\/nu12061893"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gama, M.I., Adam, S., Adams, S., Allen, H., Ashmore, C., Bailey, S., Cochrane, B., Dale, C., Daly, A., and De Sousa, G. (2022). Suitability and Allocation of Protein-Containing Foods According to Protein Tolerance in PKU: A 2022 UK National Consensus. Nutrients, 14.","DOI":"10.3390\/nu14234987"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/S0140-6736(18)30311-8","article-title":"Before the beginning: Nutrition and lifestyle in the preconception period and its importance for future health","volume":"391","author":"Stephenson","year":"2018","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1136\/adc.2005.084285","article-title":"Protein substitute dosage in PKU: How much do young patients need?","volume":"91","author":"MacDonald","year":"2006","journal-title":"Arch. Dis. Child."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/S0002-8223(99)00382-X","article-title":"Necessity of complete intake of phenylalanine-free amino acid mixture for metabolic control of phenylketonuria","volume":"99","author":"Duran","year":"1999","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_38","first-page":"1379","article-title":"Phenylketonuria treated with a high phenylalanine intake and casein-hydrolysate\/aminoacid mixtures","volume":"1","year":"1961","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"S121","DOI":"10.1007\/PL00014227","article-title":"Recommendations for protein and energy intakes by patients with phenylketonuria","volume":"155","author":"Acosta","year":"1996","journal-title":"Eur. J. Pediatr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ymgme.2013.05.017","article-title":"Tetrahydrobiopterin therapy vs phenylalanine-restricted diet: Impact on growth in PKU","volume":"109","author":"Bueno","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1515\/jpem-2015-0337","article-title":"Long-term BH4 (sapropterin) treatment of children with hyperphenylalaninemia\u2014Effect on median Phe\/Tyr ratios","volume":"29","author":"Tansek","year":"2016","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/jcap.12207","article-title":"Stress and quality of life in parents of children with phenylketonuria","volume":"31","author":"Irannejad","year":"2018","journal-title":"J. Child. Adolesc. Psychiatr. Nurs."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.dsx.2016.07.002","article-title":"Parenting a child with metabolic diseases: Impact on health related quality of life of parents","volume":"11","author":"Saraswathy","year":"2017","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/jpepsy\/jsh058","article-title":"Brief report: Predictors of parenting stress among parents of children with biochemical genetic disorders","volume":"29","author":"Waisbren","year":"2004","journal-title":"J. Pediatr. Psychol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111576","DOI":"10.1016\/j.nut.2021.111576","article-title":"Dietary treatment in Dutch children with phenylketonuria: An inventory of associated social restrictions and eating problems","volume":"97","author":"Haitjema","year":"2022","journal-title":"Nutrition"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1007\/s10545-012-9458-1","article-title":"Tetrahydrobiopterin (BH4) in PKU: Effect on dietary treatment, metabolic control, and quality of life","volume":"35","author":"Ziesch","year":"2012","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.ymgme.2013.09.015","article-title":"Evaluation of quality of life in PKU before and after introducing tetrahydrobiopterin (BH4); a prospective multi-center cohort study","volume":"110","author":"Demirdas","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/apa.13799","article-title":"Sapropterin treatment does not enhance the health-related quality of life of patients with phenylketonuria and their parents","volume":"106","author":"Feldmann","year":"2017","journal-title":"Acta Paediatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/1477-7525-11-218","article-title":"Longitudinal quality of life analysis in a phenylketonuria cohort provided sapropterin dihydrochloride","volume":"11","author":"Douglas","year":"2013","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/8904_2016_567","article-title":"Relationships Between Childhood Experiences and Adulthood Outcomes in Women with PKU: A Qualitative Analysis","volume":"32","author":"Roberts","year":"2017","journal-title":"JIMD Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Poole, G., Pinto, A., Evans, S., Ford, S., O\u2019Driscoll, M., Buckley, S., Ashmore, C., Daly, A., and MacDonald, A. (2022). Hungry for Change: The Experiences of People with PKU, and Their Caregivers, When Eating out. Nutrients, 14.","DOI":"10.3390\/nu14030626"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/16\/3603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:35:35Z","timestamp":1760128535000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/16\/3603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,17]]},"references-count":52,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["nu15163603"],"URL":"https:\/\/doi.org\/10.3390\/nu15163603","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,17]]}}}