{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T22:47:11Z","timestamp":1765234031601,"version":"3.44.0"},"reference-count":10,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100024932","name":"Children\u2019s Health Foundation","doi-asserted-by":"publisher","award":["RPAC19.02"],"award-info":[{"award-number":["RPAC19.02"]}],"id":[{"id":"10.13039\/501100024932","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,6,15]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (3-MCC-D) is an autosomal recessive disorder with a variable phenotype. Reduced 3-MCC enzyme activity results in impaired leucine metabolism causing, for example, metabolic acidosis, ketotic hypoglycaemia and carnitine deficiency. The spectrum of clinical presentation is wide, ranging from severe early-onset presentations to incidental findings in asymptomatic individuals. This report describes the case of a young girl who underwent dramatic developmental regression at 11 months of age, following a respiratory tract infection. Metabolic investigations revealed high excretions of urinary 3-methylcrotonylglycine and 3-hydroxyisovaleric acid, consistent with 3-MCC-D. Treatment was commenced immediately, including carnitine, biotin and moderate dietetic modifications. Molecular genetic investigations confirmed compound heterozygosity for two pathogenic variants in the <jats:italic>MCCC1<\/jats:italic> gene, Trp358Cysfs*13 and duplication of exons 2 and 3. Now in middle childhood, the girl is meeting all her developmental milestones and has had no metabolic decompensation in 6 years of follow-up.<\/jats:p>","DOI":"10.1136\/bcr-2024-262865","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T13:25:12Z","timestamp":1752153912000},"page":"e262865","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["3-methylcrotonyl-CoA carboxylase deficiency in a child with developmental regression and delay: call for early diagnosis and multidisciplinary approach"],"prefix":"10.1136","volume":"18","author":[{"given":"Muhammad Moazzam","family":"Gulzar","sequence":"first","affiliation":[{"name":"Paediatrics, Midland Regional Hospital Portlaoise, Portlaoise, Laois, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zulfiqar Ali","family":"Sarani","sequence":"additional","affiliation":[{"name":"Paediatrics, Midland Regional Hospital Portlaoise, Portlaoise, Laois, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Tariq","sequence":"additional","affiliation":[{"name":"Paediatrics, Midland Regional Hospital Portlaoise, Portlaoise, Laois, Ireland"},{"name":"Women\u2019s & Children\u2019s Health, University College Dublin College of Health Sciences, Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-0658","authenticated-orcid":false,"given":"Ina","family":"Knerr","sequence":"additional","affiliation":[{"name":"National Centre for Inherited Metabolic Disorders, Children\u2019s Health Ireland, Dublin, Ireland"},{"name":"Women\u2019s & Children\u2019s Health, University College Dublin College of Health Sciences, Dublin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"2025082700444127000_18.7.e262865.1","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-7-31","article-title":"3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical, enzymatic and molecular studies in 88 individuals","volume":"7","author":"Gr\u00fcnert","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"2025082700444127000_18.7.e262865.2","doi-asserted-by":"crossref","unstructured":"Knerr I , Vockley J , Gibson KM . Disorders of leucine, isoleucine, and valine metabolism. In: Blau N , Duran M , Gibson KM , et al , eds. Physician\u2019s guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. Berlin Heidelberg: Springer, 2014: 103\u201341.","DOI":"10.1007\/978-3-642-40337-8_7"},{"key":"2025082700444127000_18.7.e262865.3","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20349"},{"key":"2025082700444127000_18.7.e262865.4","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024015227863"},{"key":"2025082700444127000_18.7.e262865.5","doi-asserted-by":"publisher","DOI":"10.1007\/s004310050696"},{"key":"2025082700444127000_18.7.e262865.6","doi-asserted-by":"publisher","DOI":"10.1007\/BF02436014"},{"key":"2025082700444127000_18.7.e262865.7","doi-asserted-by":"publisher","DOI":"10.1007\/BF02436012"},{"key":"2025082700444127000_18.7.e262865.8","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/humu.9352","article-title":"3-Methylcrotonyl-CoA carboxylase deficiency: mutation analysis in 28 probands, 9 symptomatic and 19 detected by newborn screening","volume":"26","author":"Dantas","year":"2005","journal-title":"Hum Mutat"},{"key":"2025082700444127000_18.7.e262865.9","doi-asserted-by":"publisher","DOI":"10.1097\/01.gim.0000223467.60151.02"},{"key":"2025082700444127000_18.7.e262865.10","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.ymgme.2013.09.006","article-title":"Analysis of cases of 3-methylcrotonyl CoA carboxylase deficiency (3-MCCD) in the California newborn screening program reported in the state database","volume":"110","author":"Lam","year":"2013","journal-title":"Mol Genet Metab"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2024-262865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T07:44:47Z","timestamp":1756280687000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2024-262865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":10,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,10]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bcr-2024-262865"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2024-262865","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}