{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:41:56Z","timestamp":1760402516681,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Phenylketonuria (PKU) is a rare autosomal recessive condition affecting about 1 in 10,000 people in the Europe, with a higher rate in some countries, like Ireland and Italy. In Italy, newborn screening (NBS) by MS\/MS allows the diagnostic suspicion of PKU and its variants (Hyperphenylalaninemia (HPA), Tetrahydrobiopterin (BH4) synthesis deficiency, and Tetrahydrobiopterin (BH4) recycling deficiency) through the quantification of Phenylalanine (Phe) and the Phenylalanine\/Tyrosine (Phe\/Tyr) ratio in dried blood Spot (DBS) samples. Here, we report a case of an HPA whose suspicion was possible with expanded NBS, even if the normal-weight newborn was in total parenteral nutrition (TPN). It is known that TPN may present metabolic alterations, mainly for amino acids at NBS in MS\/MS, frequently causing false positives. Actually, TPN is considered a special protocol in NBS, requiring several sample collections. In particular, a DBS sample is required before TPN, at basal time point (48 h after birth) and 72 h after the end of the procedure. In the case we report, even if the first DBS sample (before TPN) resulted negative, the repeated NBS tests revealed increased levels of Phe and dramatically high Phe\/Tyr ratio. Thus, the newborn was recalled, and the NBS test was repeated several times before that HPA suspicion was confirmed by other specific biochemical tests. This case highlights the importance of Phe\/Tyr ratio, only detectable by MS\/MS analysis, in supporting the diagnostic suspicion during amino acids administration in the neonatal period.<\/jats:p>","DOI":"10.3390\/metabo10020044","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T11:01:00Z","timestamp":1579863660000},"page":"44","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Case of Suspected Hyperphenylalaninemia at Newborn Screening by Tandem Mass Spectrometry during Total Parenteral Nutrition"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-3484","authenticated-orcid":false,"given":"Damiana","family":"Pieragostino","sequence":"first","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medical, Oral and Biotechnological Sciences, University \u2018\u2018G. d\u2019Annunzio\u2019\u2019 of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-2225","authenticated-orcid":false,"given":"Ilaria","family":"Cicalini","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medicine and Aging Science, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Di Michele","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cSpirito Santo\u201d Hospital, 65100 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Fusilli","sequence":"additional","affiliation":[{"name":"Department of Maternal and Child Health, Neonatal Intensive Care Unit NICU, \u201cSpirito Santo\u201d Hospital, 65100 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Cotugno","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Bambino Ges\u00f9 Children Hospital and Research Institute, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Psychological, Health and Territory Sciences, School of Medicine and Health Sciences, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Bucci","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medicine and Aging Science, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Dionisi-Vici","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Bambino Ges\u00f9 Children Hospital and Research Institute, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liborio","family":"Stuppia","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Psychological, Health and Territory Sciences, School of Medicine and Health Sciences, \u201cG. d\u2019Annunzio\u201d University, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"De Laurenzi","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medical, Oral and Biotechnological Sciences, University \u2018\u2018G. d\u2019Annunzio\u2019\u2019 of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-0280","authenticated-orcid":false,"given":"Claudia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology (CAST), University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Department of Medicine and Aging Science, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1561S","DOI":"10.1093\/jn\/137.6.1561S","article-title":"Management of phenylketonuria and hyperphenylalaninemia","volume":"137","author":"Abadie","year":"2007","journal-title":"J. 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