{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:41:48Z","timestamp":1790358108633,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Introduction: Elevated succinylacetone (SA) is the hallmark of tyrosinemia type 1, which requires immediate treatment. Mild SA elevation has also been recently reported in maleylacetoacetate isomerase deficiency (MAAID). Methods: We report on two cases of MAAID, review clinical features of MAAID and discuss its management. Results: Both cases displayed elevated SA and normal Tyrosine levels at newborn screening. Case 1 showed intermittent SA elevation; Nitisinone and dietary treatment were started, then discontinued after the identification of two variants in the GSTZ1 gene and the definitive diagnosis of MAAID. Case 2, showing no SA elevation at the confirmatory tests and two variants in the GSTZ1 gene, did not start treatment. mRNA analysis confirmed the pathogenicity of the c.68-12G&gt;A variant, found in both patients. Discussion: MAAID should be considered in newborns showing elevated SA and no variants in the FAH gene. Our study reports for the first time the course of SA in a patient affected by MAAID. Furthermore, it expands the molecular epidemiology of this rare disease, also investigating the pathogenicity of a novel splicing mutation. Although our data argue against medical treatment in MAAID, longer follow-up data are warranted.<\/jats:p>","DOI":"10.3390\/genes16091009","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:18:49Z","timestamp":1756217929000},"page":"1009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Variants in GSTZ1 Gene Underlying Maleylacetoacetate Isomerase Deficiency: Characterization of Two New Individuals and Literature Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Ferdinando","family":"Barretta","sequence":"first","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Uomo","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"},{"name":"Department of Advanced Biomedical Science, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-649X","authenticated-orcid":false,"given":"Alessandra","family":"Verde","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Paediatrics, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Fisco","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Gallo","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Albano","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Crisci","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7774-2799","authenticated-orcid":false,"given":"Cristina","family":"Mazzaccara","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Strisciuglio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Paediatrics, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ruoppolo","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Fecarotta","sequence":"additional","affiliation":[{"name":"Department of Integrated Maternal-Fetal Care, \u201cFederico II\u201d University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Parenti","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Paediatrics, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3487-7743","authenticated-orcid":false,"given":"Giulia","family":"Frisso","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate\u2013Franco Salvatore s.c.ar.l., 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1689-4948","authenticated-orcid":false,"given":"Alessandro","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Paediatrics, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/hep.1840200513","article-title":"Hereditary tyrosinemia type I: A new clinical classification with difference in prognosis on dietary treatment","volume":"20","author":"Thomasse","year":"1994","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1750-1172-8-8","article-title":"Recommendations for the management of tyrosinaemia type 1","volume":"8","author":"Leonard","year":"2013","journal-title":"Orphanet J. 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