{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:40:08Z","timestamp":1777952408986,"version":"3.51.4"},"reference-count":17,"publisher":"BMJ","issue":"5","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2026,4,15]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    \u03b2-ureidopropionase (\u03b2UP) deficiency, caused by pathogenic variants in\n                    <jats:italic>UPB1<\/jats:italic>\n                    , is a rare autosomal recessive disorder with fewer than 60 reported cases to date. Clinical presentation is highly variable, ranging from asymptomatic individuals to severe neurodevelopmental disorders. Diagnosis relies on the detection of pyrimidine degradation metabolites, such as N-carbamyl-\u03b2-alanine (NC\u03b2A) and N-carbamyl-\u03b2-aminoisobutyrate (NC\u03b2AIBA), which are not widely available in routine clinical practice.\n                  <\/jats:p>\n                  <jats:p>\n                    We report a 7-year-old boy with early-onset developmental delay and regression, Leigh-like basal ganglia lesions on brain MRI, and persistent elevation of urinary methylmalonic acid (MMA). Muscle biopsy revealed an isolated respiratory chain complex I deficiency. Genetic testing identified two novel biallelic\n                    <jats:italic>UPB1<\/jats:italic>\n                    variants, and urinary analysis confirmed marked elevation of pyrimidine degradation metabolites, establishing the diagnosis of \u03b2UP deficiency.\n                  <\/jats:p>\n                  <jats:p>This case expands the clinical and neuroradiological spectrum of \u03b2UP deficiency and identifies elevated urinary MMA as a previously unreported finding in this disorder. Given the widespread availability of urinary organic acid analysis, MMA may represent a possibly useful and accessible biomarker to support diagnosis. \u03b2UP deficiency should be considered in the differential diagnosis of children with Leigh-like encephalopathy and unexplained MMA elevation.<\/jats:p>","DOI":"10.1136\/bcr-2026-272561","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:35:17Z","timestamp":1777898117000},"page":"e272561","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-ureidopropionase deficiency mimicking Leigh syndrome associated with methylmalonic aciduria"],"prefix":"10.1136","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-4807","authenticated-orcid":false,"given":"Giulia","family":"Ferrera","sequence":"first","affiliation":[{"name":"Child Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"},{"name":"Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Lombardy, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Boenzi","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology, Bambino Ges\u00f9 Pediatric Hospital, IRCCS, Rome, Lazio, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Lamantea","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics and Neurogenetics - Mariani Foundation Centre for Paediatric Mitochondrial Disorders, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Lombardy, Italy"},{"name":"Unit of Medical Genetics and Neurogenetics - Mariani Foundation Centre for Paediatric Mitochondrial Disorders, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ardissone","sequence":"additional","affiliation":[{"name":"Child Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Lombardy, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"2026050405351298000_19.5.e272561.1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh303"},{"key":"2026050405351298000_19.5.e272561.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.04.001"},{"key":"2026050405351298000_19.5.e272561.3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/jms.1500","article-title":"Five cases of beta-ureidopropionase deficiency detected by GC\/MS analysis of urine 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(Bacau)"},{"key":"2026050405351298000_19.5.e272561.9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.5582\/irdr.2018.01026","article-title":"Methylmalonic acidemia: Current status and research priorities","volume":"7","author":"Zhou","year":"2018","journal-title":"Intractable Rare Dis Res"},{"key":"2026050405351298000_19.5.e272561.10","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2026050405351298000_19.5.e272561.11","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-021-02029-3","article-title":"Clinical, imaging, biochemical and molecular features in Leigh syndrome: a study from the Italian network of mitochondrial diseases","volume":"16","author":"Ardissone","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"2026050405351298000_19.5.e272561.12","doi-asserted-by":"crossref","DOI":"10.1007\/s11910-016-0656-3","article-title":"Neurological Disorders Associated with Striatal Lesions: Classification and Diagnostic 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