{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:51:00Z","timestamp":1788425460576,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Health Sciences"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metab Brain Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine metabolism, in which especially high phenylalanine concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe intellectual disability, epilepsy, and behavioural problems. We aimed to investigate demographic, clinical, biochemical, and molecular genetic data in patients with phenylalanine metabolism disorder. This study included 99 predominantly Turkish patients diagnosed with phenylalanine metabolism disorder, primarily referred through newborn screening programs. These patients were evaluated at a single center over a 9-year period, from 2013 to 2021. Demographic, clinical, molecular and laboratory data were collected retrospectively. Among the 99 patients, 93 (93.9%) had hyperphenylalaninemia-phenylketonuria, 2 (2.0%) had tetrahydrobiopterin metabolism disorders [one due to 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency and the other due to dihydropteridine reductase (DHPR) deficiency], 3 (3.0%) had maternal PKU syndrome (one of whom also had mild phenylketonuria), and 1 (1.0%) had transient hyperphenylalaninemia. The majority of patients belonged to the mild hyperphenylalaninemia-not requiring treatment group. A total of 33 different alleles and 40 genotypes (59.6% compound heterozygous) were identified in the <jats:italic>PAH<\/jats:italic> gene, with missense variants accounting for the largest proportion (72.7%). The most frequent <jats:italic>PAH<\/jats:italic> gene variants were c.898G\u2009&gt;\u2009T p.(Ala300Ser) (14.9%), c.1066-11G\u2009&gt;\u2009A (8.5%), and c.1208C\u2009&gt;\u2009T p.(Ala403Val) (8.5%), while the most common genotypes were c.898G\u2009&gt;\u2009T p.(Ala300Ser)\/c.898G\u2009&gt;\u2009T p.(Ala300Ser) (6.4%) and c.898G\u2009&gt;\u2009T p.(Ala300Ser) \/c.1066-11G\u2009&gt;\u2009A (6.4%), respectively. Among patients with mild hyperphenylalaninemia-not requiring treatment, the predominant genotypes were c.898G\u2009&gt;\u2009T p.(Ala300Ser)\/c.898G\u2009&gt;\u2009T p.(Ala300Ser) (11.1%), c.898G\u2009&gt;\u2009T p.(Ala300Ser)\/c.1066-11G\u2009&gt;\u2009A (11.1%), and c.1208C\u2009&gt;\u2009T p.(Ala403Val)\/c.1208C\u2009&gt;\u2009T p.(Ala403Val) (7.4%), whereas c.842C\u2009&gt;\u2009T p.(Pro281Leu)\/c.842C\u2009&gt;\u2009T p.(Pro281Leu) (33.3%) was frequently observed in classic PKU patients. The national newborn screening program has significantly improved the prognosis and quality of life for patients through early diagnosis and timely treatment. While the prevalence of hyperphenylalaninemia-phenylketonuria remains high in Turkey, the higher frequency of the hyperphenylalaninemia-not requiring treatment group, compared to European and Asian countries, is considered a favorable outcome. Additionally, the PAH genotype is identified as the primary determinant of the PKU phenotype.<\/jats:p>","DOI":"10.1007\/s11011-025-01582-1","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T06:51:28Z","timestamp":1745823088000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genotypic and phenotypic characteristics of Turkish patients with phenylalanine metabolism disorders"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2123-7045","authenticated-orcid":false,"given":"Fatma-Nur","family":"Kuzucu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1401-5233","authenticated-orcid":false,"given":"Mustafa","family":"Kilic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-3808","authenticated-orcid":false,"given":"Abdullah","family":"Sezer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6079-5517","authenticated-orcid":false,"given":"Selen","family":"Has-Ozhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1918-2575","authenticated-orcid":false,"given":"Harun","family":"Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-6727","authenticated-orcid":false,"given":"Tuba","family":"Celen-Yoldas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2668-671X","authenticated-orcid":false,"given":"Fatma-Nese","family":"Onat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5459-3580","authenticated-orcid":false,"given":"Melike","family":"Uyanik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"1582_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-024-10892-5","author":"\u00d6 Balasar","year":"2024","unstructured":"Balasar \u00d6, Kad\u0131o\u011flu Y\u0131lmaz B, Ba\u015fdemirci M, Ko\u00e7akEker H, Eser\u00c7avdartepe B, \u015eim\u015fek L, Tun\u00e7ez E et al (2024) Assessment of pathogenic variants in the PAH gene and genotype-phenotype correlation in phenylketonuria patients from Turkey. 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All co-authors reviewed the final approval of the version from prior to submission. All authors have been involved in (a) conception and design, or analysis and interpretation of data and (b) drafting the case or revising it critically for important intellectual content and agree to submission. All authors have provided the information on \u2018Compliance with Ethics Guidelines\u2019.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"193"}}