{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:55:03Z","timestamp":1787579703831,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Combined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism caused by a deficiency in mitochondrial malonyl\u2010CoA synthetase, the enzyme responsible for activating malonic acid (MA) to malonyl\u2010CoA, a precursor of lipoic acid. The clinical phenotype is highly heterogeneous, ranging from asymptomatic cases to severe neurological impairment. We describe a patient affected by CMAMMA. The patient presented in the neonatal period with hyperinsulinemic hypoglycemia. Urinary organic acid analysis revealed elevated levels of both malonic and methylmalonic acids. The diagnosis of CMAMMA was confirmed through molecular testing of the\n                    <jats:italic>ACSF3<\/jats:italic>\n                    gene. Levels of both lipoylated pyruvate dehydrogenase (PDH) and \u03b1\u2010ketoglutarate dehydrogenase (\u03b1KGDH) were decreased. Given the role of lipoic acid in regulating insulin secretion, the involvement of impaired mitochondrial lipoic acid biosynthesis in the clinical presentation of hyperinsulinemic hypoglycemia cannot be excluded. We describe a case of CMAMMA associated with hyperinsulinemic hypoglycemia. While a definitive association between CMAMMA and hyperinsulinism cannot be established based on a single case, the observed reduction in lipoic acid levels may suggest a mechanistic connection between the two disorders. We suggest considering urinary organic acid testing in patients with hyperinsulinism, especially when the cause is unknown.\n                  <\/jats:p>","DOI":"10.1002\/jmd2.70045","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T03:09:58Z","timestamp":1759115398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Deep Clinical and Biochemical Characterization of a Patient With Combined Malonic and Methylmalonic Aciduria (CMAMMA)"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-652X","authenticated-orcid":false,"given":"Vincenza","family":"Gragnaniello","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Galderisi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-4843","authenticated-orcid":false,"given":"Sara","family":"Tucci","sequence":"additional","affiliation":[{"name":"Pharmacy Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Doimo","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Department of Women and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Caterino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-2034","authenticated-orcid":false,"given":"Christian","family":"Loro","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cazzorla","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Ruoppolo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Salviati","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Department of Women and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-137X","authenticated-orcid":false,"given":"Alberto B.","family":"Burlina","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.291591"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12032"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns8030047"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010014\u20100130\u20108"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.751895"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102011\u2010100230"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.908"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u20101299\u20107"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073799"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2010.02.020"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.03.057"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.901338"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2020.02.079"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010006\u20100265\u20109"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15010018"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.04.009"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2019.07.012"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701486200"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170416"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.03.006"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151171"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.70045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T07:57:42Z","timestamp":1764143862000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.70045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jmd2.70045"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.70045","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,28]]},"assertion":[{"value":"2025-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70045"}}