{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:20:41Z","timestamp":1789503641341,"version":"build-2803163510"},"reference-count":11,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2023,10,16]]},"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:p>Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) is the main enzyme involved in ketogenesis. It is an essential enzyme for the catalysis of \u03b2-oxidation-derived-acetyl-CoA and acetoacetyl Co-A to produce \u03b2-hydroxy-\u03b2-methylglutaryl-CoA (HMG-CoA) and free coenzyme A.<\/jats:p>\n               <jats:p>The deficiency of this enzyme (3-hydoxy-3-methylglutaryl-CoA synthase) is a very rare metabolic disorder with limited cases described in the literature. The manifestations of this disease include hypoketotic hypoglycaemia, metabolic acidosis, lethargy, hepatomegaly with fatty liver and encephalopathy.<\/jats:p>\n               <jats:p>We report a middle childhood male who presented with hepatosplenomegaly, lymphadenopathy and bicytopenia. The case was diagnosed by the whole exome sequencing which revealed a homozygous missense variant of uncertain significance in HMGCS2 gene.<\/jats:p>","DOI":"10.1136\/bcr-2023-257011","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T11:15:47Z","timestamp":1699269347000},"page":"e257011","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) deficiency: a rare case with bicytopenia and coagulopathy"],"prefix":"10.1136","volume":"16","author":[{"given":"Dalia","family":"El-Sayed","sequence":"first","affiliation":[{"name":"Pediatrics, Cairo University Kasr Alainy Faculty of Medicine, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa","family":"El-Karaksy","sequence":"additional","affiliation":[{"name":"Pediatrics, Cairo University Kasr Alainy Faculty of Medicine, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4275-4524","authenticated-orcid":false,"given":"Yasser","family":"Wali","sequence":"additional","affiliation":[{"name":"Department of Child Health, Sultan Qaboos University, Muscat, Oman"},{"name":"Alexandria University Faculty of Medicine, Alexandria, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5972-7712","authenticated-orcid":false,"given":"Ilham","family":"Youssry","sequence":"additional","affiliation":[{"name":"Pediatrics, Cairo University Kasr Alainy Faculty of Medicine, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,11,6]]},"reference":[{"key":"2025082702561334000_16.11.e257011.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.11.003"},{"key":"2025082702561334000_16.11.e257011.2","doi-asserted-by":"crossref","first-page":"816779","DOI":"10.3389\/fgene.2021.816779","article-title":"Clinical, biochemical, molecular, and outcome features of mitochondrial 3-hydroxy-3-methylglutaryl-coa synthase deficiency in 10 Chinese patients","volume":"12","author":"Wu","year":"2021","journal-title":"Front Genet"},{"key":"2025082702561334000_16.11.e257011.3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cca.2020.04.004","article-title":"Clinical, biochemical, molecular and therapeutic characteristics of four new patients of mitochondrial 3-hydroxy-3-methylglutaryl-coa synthase deficiency","volume":"509","author":"Wang","year":"2020","journal-title":"Clin Chim Acta"},{"key":"2025082702561334000_16.11.e257011.4","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1002\/ajmg.a.61590","article-title":"Expanding the clinical spectrum of mitochondrial 3-hydroxy-3-methylglutaryl-coa synthase deficiency with Turkish cases harboring novel HMGCS2 gene mutations and literature review","volume":"182","author":"K\u0131l\u0131\u00e7","year":"2020","journal-title":"Am J Med Genet A"},{"key":"2025082702561334000_16.11.e257011.5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00431-002-1110-x","article-title":"Mitochondrial HMG-CoA synthase deficiency: identification of two further patients carrying two novel mutations","volume":"162","author":"Wolf","year":"2003","journal-title":"Eur J Pediatr"},{"key":"2025082702561334000_16.11.e257011.6","doi-asserted-by":"crossref","unstructured":"Morris AA . Disorders of Ketogenesis and Ketolysis. In: Inborn Metabolic Diseases: Diagnosis and Treatment. 2016: 215\u201321. doi:10.1007\/978-3-662-49771-5","DOI":"10.1007\/978-3-662-49771-5_13"},{"key":"2025082702561334000_16.11.e257011.7","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.3390\/ijms19041010","article-title":"Human mitochondrial HMG-CoA synthase deficiency: role of enzyme dimerization surface and characterization of three new patients","volume":"19","author":"Puisac","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2025082702561334000_16.11.e257011.8","first-page":"63","article-title":"Mitochondrial 3-hydroxy-3-methylglutaryl-coa synthase deficiency: unique presenting laboratory values and a review of biochemical and clinical features","volume":"40","author":"Conboy","year":"2018","journal-title":"JIMD Rep"},{"key":"2025082702561334000_16.11.e257011.9","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0550-8"},{"key":"2025082702561334000_16.11.e257011.10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.5582\/irdr.2016.01018","article-title":"Hemophagocytic lymphohistiocytosis: a rare cause of recurrent encephalopathy","volume":"5","author":"Sulaiman","year":"2016","journal-title":"Intractable Rare Dis Res"},{"key":"2025082702561334000_16.11.e257011.11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41392-021-00570-y","article-title":"Fructose drives mitochondrial metabolic reprogramming in podocytes via HMGCS2-stimulated fatty acid degradation","volume":"6","author":"Fang","year":"2021","journal-title":"Signal Transduct Target Ther"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2023-257011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:56:56Z","timestamp":1756288616000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2023-257011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":11,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11,6]]},"published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1136\/bcr-2023-257011"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2023-257011","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11]]}}}