{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:00:26Z","timestamp":1760144426246,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,20]],"date-time":"2024-04-20T00:00:00Z","timestamp":1713571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Joint Programme on Rare Diseases","award":["EJPRD19-145 GENOMIT I4695-B"],"award-info":[{"award-number":["EJPRD19-145 GENOMIT I4695-B"]}]},{"name":"Austrian Science Fund","award":["EJPRD19-145 GENOMIT I4695-B"],"award-info":[{"award-number":["EJPRD19-145 GENOMIT I4695-B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Citric acid cycle deficiencies are extremely rare due to their central role in energy metabolism. The ACO2 gene encodes the mitochondrial isoform of aconitase (aconitase 2), the second enzyme of the citric acid cycle. Approximately 100 patients with aconitase 2 deficiency have been reported with a variety of symptoms, including intellectual disability, hypotonia, optic nerve atrophy, cortical atrophy, cerebellar atrophy, and seizures. In this study, a homozygous deletion in the ACO2 gene in two brothers with reduced aconitase 2 activity in fibroblasts has been described with symptoms including truncal hypotonia, optic atrophy, hyperopia, astigmatism, and cerebellar atrophy. In an in vivo trial, triheptanoin was used to bypass the defective aconitase 2 and fill up the citric acid cycle. Motor abilities in both patients improved.<\/jats:p>","DOI":"10.3390\/metabo14040238","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T06:10:18Z","timestamp":1713766218000},"page":"238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anaplerotic Therapy Using Triheptanoin in Two Brothers Suffering from Aconitase 2 Deficiency"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0323-7163","authenticated-orcid":false,"given":"Maximilian","family":"Penkl","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Kinder- und Jugendmedizin, Universit\u00e4tsklinikum M\u00fcnster, Albert-Schweizer-Campus 1, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-336X","authenticated-orcid":false,"given":"Johannes A.","family":"Mayr","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinik f\u00fcr Kinder- und Jugendheilkunde, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), M\u00fcllner Hauptstra\u00dfe 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-8258","authenticated-orcid":false,"given":"Ren\u00e9 G.","family":"Feichtinger","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinik f\u00fcr Kinder- und Jugendheilkunde, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), M\u00fcllner Hauptstra\u00dfe 48, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-9517","authenticated-orcid":false,"given":"Ralf","family":"Reilmann","sequence":"additional","affiliation":[{"name":"George-Huntington-Institut, Wilhelm-Schickard-Stra\u00dfe 15, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otfried","family":"Debus","sequence":"additional","affiliation":[{"name":"Clemenshospital M\u00fcnster, Klinik f\u00fcr Kinder- und Jugendmedizin, D\u00fcesbergweg 124, 48153 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Fobker","sequence":"additional","affiliation":[{"name":"Zentrale Einrichtung UKM Labor, Universit\u00e4tsklinikum M\u00fcnster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-3401","authenticated-orcid":false,"given":"Anja","family":"Penkl","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder- und Jugendmedizin, Universit\u00e4tsklinikum M\u00fcnster, Albert-Schweizer-Campus 1, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7220-7594","authenticated-orcid":false,"given":"Janine","family":"Reunert","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder- und Jugendmedizin, Universit\u00e4tsklinikum M\u00fcnster, Albert-Schweizer-Campus 1, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Rust","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder- und Jugendmedizin, Universit\u00e4tsklinikum M\u00fcnster, Albert-Schweizer-Campus 1, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinder- und Jugendmedizin, Universit\u00e4tsklinikum M\u00fcnster, Albert-Schweizer-Campus 1, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ymgme.2016.03.004","article-title":"Functional Cellular Analyses Reveal Energy Metabolism Defect and Mitochondrial DNA Depletion in a Case of Mitochondrial Aconitase Deficiency","volume":"118","author":"Sadat","year":"2016","journal-title":"Mol. 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