{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:27:46Z","timestamp":1787570866577,"version":"build-2736575974"},"reference-count":21,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2026,8,14]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    A female toddler born to consanguineous parents presented with severe Epstein-Barr virus hepatitis, hyperferritinaemia and severe neutropenia, initially suggesting haemophagocytic lymphohistiocytosis. Metabolic screening revealed elevated very-long-chain fatty acids and dicarboxylic aciduria, mimicking a peroxisomal disorder. Brain MRI demonstrated cortical thickening and smoothing that were more pronounced in both temporal lobes, with poorly formed gyri characteristic of pachygyria-lissencephaly, underlying subcortical white matter thinning affecting the temporo-insular parenchyma and moderate cerebellar hypoplasia. Exome sequencing identified a homozygous pathogenic\n                    <jats:italic>EIF2AK3<\/jats:italic>\n                    mutation (c.3193C&gt;T, p.Arg1065*), confirming Wolcott-Rallison syndrome. This case expands the Wolcott-Rallison syndrome phenotype: neonatal diabetes and skeletal dysplasia were absent at presentation, and the neuroimaging demonstrated previously unreported patterns. It highlights that severe viral infections can create misleading biochemical patterns in patients with endoplasmic reticulum stress-pathway defects, emphasising the importance of comprehensive genetic testing.\n                  <\/jats:p>","DOI":"10.1136\/bcr-2025-269660","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:15:16Z","timestamp":1787570116000},"page":"e269660","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Atypical presentation of Wolcott-Rallison syndrome with severe Epstein-Barr virus hepatitis, secondary peroxisomal dysfunction and novel neuroimaging features"],"prefix":"10.1136","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4161-7592","authenticated-orcid":false,"given":"Mossaab","family":"Hassoun","sequence":"first","affiliation":[{"name":"Pediatrics, ALSALAM Specialist Hospital, Manama, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Malas","sequence":"additional","affiliation":[{"name":"Pediatrics, New Mazloum Hospital, Tripoli, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinane","family":"Khaled","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology, Haykel Hospital, Tripoli, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Hassoun","sequence":"additional","affiliation":[{"name":"NICU, Royale Hayat Hospital, Hawally, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"2026082404150829000_19.8.e269660.1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15834"},{"key":"2026082404150829000_19.8.e269660.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1137"},{"key":"2026082404150829000_19.8.e269660.3","doi-asserted-by":"publisher","DOI":"10.1038\/78085"},{"key":"2026082404150829000_19.8.e269660.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2009.00591.x"},{"key":"2026082404150829000_19.8.e269660.5","doi-asserted-by":"crossref","DOI":"10.1186\/1750-1172-5-29","article-title":"Wolcott-Rallison syndrome","volume":"5","author":"Julier","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"2026082404150829000_19.8.e269660.6","doi-asserted-by":"publisher","DOI":"10.1007\/PL00008394"},{"key":"2026082404150829000_19.8.e269660.7","doi-asserted-by":"crossref","first-page":"238","DOI":"10.5114\/pedm.2022.118325","article-title":"Wolcott-Rallison syndrome: a case series of three patients","volume":"28","author":"Memon","year":"2022","journal-title":"Pediatr Endocrinol Diabetes Metab"},{"key":"2026082404150829000_19.8.e269660.8","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000369804","article-title":"Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort","volume":"83","author":"Habeb","year":"2015","journal-title":"Horm Res Paediatr"},{"key":"2026082404150829000_19.8.e269660.9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/SHK.0000000000001048","article-title":"Hemophagocytic lymphohistiocytosis: potentially underdiagnosed in intensive care units","volume":"50","author":"Lachmann","year":"2018","journal-title":"Shock"},{"key":"2026082404150829000_19.8.e269660.10","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jiph.2019.11.009","article-title":"Effects of Epstein-Barr virus infection on liver function in children","volume":"13","author":"Zhang","year":"2020","journal-title":"J Infect Public Health"},{"key":"2026082404150829000_19.8.e269660.11","doi-asserted-by":"crossref","DOI":"10.1186\/s43066-023-00262-y","article-title":"Epstein-Barr virus and cytomegalovirus coinfection in Egyptian COVID-19 patients","volume":"13","author":"Barakat","year":"2023","journal-title":"Egypt Liver J"},{"key":"2026082404150829000_19.8.e269660.12","doi-asserted-by":"crossref","DOI":"10.1038\/s42003-022-03867-y","article-title":"Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response","volume":"5","author":"Weinhofer","year":"2022","journal-title":"Commun Biol"},{"key":"2026082404150829000_19.8.e269660.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.11.015"},{"key":"2026082404150829000_19.8.e269660.14","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s13312-016-0913-1","article-title":"Metabolic liver diseases presenting as acute liver failure in children","volume":"53","author":"Alam","year":"2016","journal-title":"Indian Pediatr"},{"key":"2026082404150829000_19.8.e269660.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(72)80596-1"},{"key":"2026082404150829000_19.8.e269660.16","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00105-9"},{"key":"2026082404150829000_19.8.e269660.17","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/pedi.12089","article-title":"EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome","volume":"15","author":"Jahnavi","year":"2014","journal-title":"Pediatr Diabetes"},{"key":"2026082404150829000_19.8.e269660.18","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.9.685"},{"key":"2026082404150829000_19.8.e269660.19","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.7.1876"},{"key":"2026082404150829000_19.8.e269660.20","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00167-21","article-title":"Human cytomegalovirus uses a host stress response to balance the elongation of saturated\/monounsaturated and polyunsaturated very-long-chain fatty acids","volume":"12","author":"Xi","year":"2021","journal-title":"MBio"},{"key":"2026082404150829000_19.8.e269660.21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1182\/blood.V92.1.291.413k34_291_299","article-title":"Epstein-Barr virus infects and induces apoptosis in human neutrophils","volume":"92","author":"Larochelle","year":"1998","journal-title":"Blood"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2025-269660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:15:18Z","timestamp":1787570118000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2025-269660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":21,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,24]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/bcr-2025-269660"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2025-269660","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}