{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:23:47Z","timestamp":1787660627516,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Type VIII 3\u2010methylglutaconic aciduria (MGCA8) is a neurodegenerative disorder which involves biallelic pathogenic variants of\n                      <jats:italic>HTRA2<\/jats:italic>\n                      . This gene encodes a mitochondrial serine protease responsible for apoptosis regulation and mitochondrial proteins' quality. Clinical manifestations include dysfunctional muscle tone, movement disorder, severe encephalopathy, epileptic seizures, dysautonomia, feeding difficulty, intermittent neutropenia, bradycardia, and recurrent apneas, often progressing into respiratory failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Report<\/jats:title>\n                    <jats:p>\n                      We describe a newborn presenting with abnormal muscle tone, progressive dystonic movements, recurrent apneas, feeding difficulties, and epileptic seizures. Biochemical analysis revealed a markedly elevated urinary 3\u2010methylglutaconic acid, and genetic test identified biallelic pathogenic variant in\n                      <jats:italic>HTRA2<\/jats:italic>\n                      . Brain MRI revealed progressive brain atrophy, thalamic hypoplasia, and ventriculomegaly. EEG recordings found organizational abnormalities that turned into epileptic spasms. Despite intensive care, the patient suffered rapid neurological decline and died following a prolonged apnea episode. Thereafter the family had another infant diagnosed with the same biallelic pathogenic variant in\n                      <jats:italic>HTRA2<\/jats:italic>\n                      , that died a few days after birth due to respiratory failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      MGCA8 is a lethal condition characterized by loss\u2010of\u2010function biallelic mutations in\n                      <jats:italic>HTRA2<\/jats:italic>\n                      , which lead to mitochondrial dysfunction and altered apoptosis regulation, especially in the brain. High levels of 3\u2010methylglutaconic acid in urine are one important early diagnostic marker, when associated with a consistent clinical phenotype. Our report contributes to the limited existing case series and provides a detailed characterization of the EEG findings associated with this rare condition.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70278","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T08:00:16Z","timestamp":1786521616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Clinical and Neurophysiological Insights in Neonatal\u2010Onset 3\u2010Methylglutaconic Aciduria Type\n                    <scp>VIII<\/scp>\n                    due to\n                    <i>HTRA2<\/i>\n                    Mutations"],"prefix":"10.1002","volume":"14","author":[{"given":"Barbara","family":"Belmessieri","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9365-8335","authenticated-orcid":false,"given":"Sara","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-9103","authenticated-orcid":false,"given":"Laura","family":"Malerba","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Martelli","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-4330","authenticated-orcid":false,"given":"Lucio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Plumari","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6346-1988","authenticated-orcid":false,"given":"Edoardo","family":"Errichiello","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics University of Pavia  Pavia Italy"},{"name":"Neurogenetics Research Center IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8801-5498","authenticated-orcid":false,"given":"Patrizia","family":"Accorsi","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107531"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1298574"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2021.08.016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100038\u20101667345"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102016\u2010103922"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010016\u20109977\u20102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn096"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1717"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151272698"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1503105112"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419581111"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.10.030"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104365"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70278","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70278","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70278","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:40:03Z","timestamp":1787658003000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":14,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/mgg3.70278"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70278","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70278"}}