{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:48:51Z","timestamp":1782272931432,"version":"3.54.5"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Since January 2023, the Russian Federation has implemented expanded neonatal screening for 36 hereditary disorders, which has changed the diagnostic algorithm for hyperphenylalaninemia\/phenylketonuria (HPA\/PKU) by introducing tandem mass spectrometry (MS\/MS) on the second day of life, followed by confirmatory biochemical and molecular testing in newborns at risk. We analyzed 1247 newborns aged 5\u201315 days with elevated phenylalanine levels (\u2265120 \u00b5mol\/L) and a phenylalanine to tyrosine ratio of at least 1 detected during the first stage of screening using MS\/MS. At the reference center, newborns underwent repeat biochemical testing and stepwise molecular analysis of HPA-associated genes. Two pathogenic variants in HPA-associated genes were identified in 538 newborns, including 534 newborns with biallelic pathogenic variants in PAH and 4 with BH4-deficient forms (PTS, QDPR). The incidence of molecularly confirmed HPA was 1:4518 newborns (95% CI: 1:4152\u20131:4925). The PAH variant spectrum was dominated by p.Arg408Trp (c.1222C&gt;T) (33.4%). Genotype-based analysis indicated that 73 newborns (13.7%) were likely responsive to cofactor therapy, whereas 222 (41.6%) were potentially responsive. These findings define the molecular epidemiology of HPA in Russia and support early genetic stratification for diagnosis and treatment.<\/jats:p>","DOI":"10.3390\/ijms27125597","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Genetic and Biochemical Characterization of Hyperphenylalaninemia Based on Expanded Neonatal Screening Data from 2023 to 2024 in the Russian Federation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0132-106X","authenticated-orcid":false,"given":"Ekaterina E.","family":"Lotnik","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena L.","family":"Chukhrova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina V.","family":"Ryadninskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varvara A.","family":"Kadnikova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina Y.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina V.","family":"Baydakova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4241-3301","authenticated-orcid":false,"given":"Andrey R.","family":"Osadchii","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga V.","family":"Anisimova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei V.","family":"Voronin","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey I.","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-4171","authenticated-orcid":false,"given":"Kirill V.","family":"Savostyanov","sequence":"additional","affiliation":[{"name":"National Medical Research Centre for Children\u2019s Health, Lomonosovskiy Prospekt, 2 b.1, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanil S.","family":"Bilalov","sequence":"additional","affiliation":[{"name":"Republican Medical Genetic Centre, Gafuri St., 74, 450076 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1568-3217","authenticated-orcid":false,"given":"Alexander L.","family":"Koroteev","sequence":"additional","affiliation":[{"name":"Diagnostic Centre (Medical Genetic), Tobolskaya St., 5A, 194044 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Y.","family":"Trofimov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov, Akademika Oparina St., 4, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana A.","family":"Bairova","sequence":"additional","affiliation":[{"name":"Scientific Centre for Family Health and Human Reproduction Problems, Timiryazeva St., 16, 664003 Irkutsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara N.","family":"Seitova","sequence":"additional","affiliation":[{"name":"Tomsk National Research Medical Centre of the Russian Academy of Sciences, Naberezhnaya Reki Ushaiki St., 10, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei V.","family":"Mordanov","sequence":"additional","affiliation":[{"name":"Laboratory Department of the Medical Genetic Center, Rostov State Medical University, Nakhichevanskiy per., 29, 344022 Rostov-na-Donu, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana A.","family":"Matulevich","sequence":"additional","affiliation":[{"name":"Scientific Research Institute-Ochapovsky Regional Clinical Hospital No. 1 of the Ministry of Health of the Krasnodar Region, No. 167, 1 Maya St., 350086 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1451-5758","authenticated-orcid":false,"given":"Tatyana A.","family":"Golikhina","sequence":"additional","affiliation":[{"name":"Scientific Research Institute-Ochapovsky Regional Clinical Hospital No. 1 of the Ministry of Health of the Krasnodar Region, No. 167, 1 Maya St., 350086 Krasnodar, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena B.","family":"Nikolaeva","sequence":"additional","affiliation":[{"name":"Clinical Diagnostic Centre \u201cMother and Child Healthcare\u201d, Flotskaya St., 52, 620067 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander V.","family":"Polyakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-1303","authenticated-orcid":false,"given":"Olga A.","family":"Shchagina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechie Str., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"ref_1","unstructured":"(2025, June 01). 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