{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:32:23Z","timestamp":1784629943947,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"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>Phenylketonuria is an inherited metabolic disorder that leads to neurobehavioral dysfunction. The main treatment is a low-phenylalanine diet and\/or the cofactor tetrahydrobiopterin. Regular outpatient follow-up care and measurement of the phenylalanine levels in the blood are required. We aimed to analyze the economic burden of phenylketonuria on families and the state. The patients with phenylketonuria were divided into three groups according to their treatment: a low-phenylalanine diet group (n = 50), a tetrahydrobiopterin group (n = 44), and a group taking tetrahydrobiopterin together with the diet (n = 25). A comparative cost analysis was carried out. The annual economic burden to the state was calculated to average EUR 18,801 \u00b1 15,345 and was lowest in the diet group, then in the tetrahydrobiopterin group, and highest in the tetrahydrobiopterin + diet group (p &lt; 0.001). Out-of-pocket costs amounted to EUR 1531 \u00b1 1173 per year, and indirect losses averaged EUR 2125 \u00b1 1930 per year for all families. The economic loss was significantly lower in the families taking tetrahydrobiopterin than in the other groups (p = 0.001). The combined use of medical nutrition and BH4 treatments has been shown to increase the economic burden on the state. Reimbursing low-protein products and increasing the number of patients eligible for financial allowances may reduce the economic burden on families.<\/jats:p>","DOI":"10.3390\/nu16101444","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:34:01Z","timestamp":1715571241000},"page":"1444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of Cost Analysis in Patients with Tetrahydrobiopterin-Responsive and Non-Responsive Phenylketonuria in Turkey"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8783-0514","authenticated-orcid":false,"given":"Merve","family":"Karaca Sahin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Cigdem","family":"Aktuglu Zeybek","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanyel","family":"Zubarioglu","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Serif","family":"Cansever","sequence":"additional","affiliation":[{"name":"Division of Medical Laboratory Techniques, Department of Medical Documentation and Techniques, The Vocational School of Health Services, Istanbul University-Cerrahpasa, 34295 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5594","authenticated-orcid":false,"given":"Ertugrul","family":"K\u0131yk\u0131m","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolism, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1097\/GIM.0b013e3182141b48","article-title":"Phenylalanine hydroxylase deficiency","volume":"13","author":"Mitchell","year":"2011","journal-title":"Genet. Med."},{"key":"ref_2","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_3","unstructured":"Scriber, C.R. (2001). The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ymgme.2009.10.016","article-title":"Pathogenesis of cognitive dysfunction in phenylketonuria: Review of hypotheses","volume":"99","author":"Hoeksma","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1136\/adc.65.5.472","article-title":"Intelligence and quality of dietary treatment in phenylketonuria","volume":"65","author":"Smith","year":"1990","journal-title":"Arch. Dis. Child."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s10545-007-0666-z","article-title":"Expanded newborn screening in Europe 2007","volume":"30","author":"Bodamer","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s10545-007-0644-5","article-title":"Neonatal screening in Europe; the situation in 2004","volume":"30","author":"Loeber","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_8","first-page":"3","article-title":"Expanded newborn screening experience in Istanbul","volume":"30","author":"Demirkol","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/jcla.21645","article-title":"The development and organization of newborn screening programs in Turkey","volume":"28","author":"Tezel","year":"2014","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_10","unstructured":"(2023, July 09). Halk Sa\u011fl\u0131\u011f\u0131 Genel M\u00fcd\u00fcrl\u00fc\u011f\u00fc, \u00c7ocuk ve Ergen Sa\u011fl\u0131\u011f\u0131 Dairesi Ba\u015fkanl\u0131\u011f\u0131 Yenido\u011fan Metabolik ve Endokrin Tarama Program\u0131, Available online: https:\/\/hsgm.saglik.gov.tr\/tr\/tarama-programlari\/ntp.html."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/humu.22980","article-title":"Genetics of Phenylketonuria: Then and Now","volume":"37","author":"Blau","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s10038-018-0529-5","article-title":"Tetrahydrobipterin-responsive phenylalanine hydroxylase deficiency","volume":"64","author":"Kure","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ymgme.2009.01.002","article-title":"Optimizing the use of sapropterin (BH4) in the management of phenylketonuria","volume":"96","author":"Blau","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ymgme.2007.09.017","article-title":"Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH4) in phenylketonuria and its use in treatment","volume":"92","author":"Levy","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/1541-4337.12057","article-title":"Strategies Used in Production of Phenylalanine-Free Foods for PKU Management","volume":"13","author":"Soltanizadeh","year":"2014","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/ejcn.2017.102","article-title":"Dietary patterns, cost and compliance with low-protein diet of phenylketonuria and other inherited metabolic diseases","volume":"72","author":"Puda","year":"2018","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1111\/j.1651-2227.2002.tb02853.x","article-title":"Homocysteine and other vascular risk factors in patients with phenylketonuria on a diet","volume":"91","author":"Schulpis","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3389\/fpsyt.2019.00561","article-title":"Psychiatric and Cognitive Aspects of Phenylketonuria: The Limitations of Diet and Promise of New Treatments","volume":"10","author":"Ashe","year":"2019","journal-title":"Front. Psychiatry"},{"key":"ref_21","unstructured":"(2023, July 09). Sosyal Sigortalar ve Genel Sa\u011fl\u0131k Sigortas\u0131 Kanunu Resmi Gazete 2006, Available online: https:\/\/www.resmigazete.gov.tr\/eskiler\/2006\/06\/20060616-1.htm."},{"key":"ref_22","unstructured":"(2023, July 09). \u00c7ocuklar i\u00e7in \u00d6zel Gereksinim De\u011ferlendirmesi Hakk\u0131nda Y\u00f6netmelik, Available online: https:\/\/www.resmigazete.gov.tr\/eskiler\/2019\/02\/20190220-1.htm."},{"key":"ref_23","unstructured":"(2023, July 09). Sosyal G\u00fcvenlik Kurumu Sa\u011fl\u0131k Uygulama Tebli\u011fi, Available online: https:\/\/www.mevzuat.gov.tr\/mevzuat?MevzuatNo=17229&MevzuatTur=9&MevzuatTertip=5."},{"key":"ref_24","unstructured":"(2023, July 09). Engelli Bireyler i\u00e7in Bilgilendirme Rehberi, Available online: https:\/\/www.aile.gov.tr\/media\/131394\/engelli_bireyler_icin_bilgilendirme_rehberi.pdf."},{"key":"ref_25","unstructured":"ESPKU (2023, July 09). PKU: Closing the Gaps in Care. Available online: https:\/\/www.espku.org\/wp-content\/uploads\/2015\/06\/PKU_report_FINAL_v2_nomarks.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ymgme.2011.12.004","article-title":"Diet in phenylketonuria: A snapshot of special dietary costs and reimbursement systems in 10 international centers","volume":"105","author":"Dokoupil","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ymgme.2009.09.005","article-title":"Management of phenylketonuria in Europe: Survey results from 19 countries","volume":"99","author":"Blau","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10545-016-9995-0","article-title":"Household financial burden of phenylketonuria and its impact on treatment in China: A cross-sectional study","volume":"40","author":"Wang","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgmr.2016.08.008","article-title":"The personal burden for caregivers of children with phenylketonuria: A cross-sectional study investigating time burden and costs in the UK","volume":"9","author":"MacDonald","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ymgme.2013.05.003","article-title":"The time consuming nature of phenylketonuria: A cross-sectional study investigating time burden and costs of phenylketonuria in the Netherlands","volume":"109","author":"Eijgelshoven","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1007\/s00296-011-1894-y","article-title":"Economic impact of juvenile idiopathic arthritis and familial Mediterranean fever","volume":"32","author":"Yucel","year":"2012","journal-title":"Rheumatol. Int."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/10\/1444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:00Z","timestamp":1760107440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/10\/1444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,10]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["nu16101444"],"URL":"https:\/\/doi.org\/10.3390\/nu16101444","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,10]]}}}