{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:50:13Z","timestamp":1791481813591,"version":"4.3.4"},"reference-count":19,"publisher":"Walter de Gruyter GmbH","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2026-0162_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Mitchell\u2013Riley syndrome (MRS) is a rare autosomal recessive disorder caused by pathogenic variants in the\n                      <jats:italic>RFX6<\/jats:italic>\n                      gene and characterized by neonatal diabetes, pancreatic hypoplasia with exocrine insufficiency, intestinal atresia, and hepatobiliary abnormalities. Despite increasing recognition of the syndrome, the number of reported cases remains limited and clinical management remains challenging. We aimed to report a preterm infant with an extremely low birth weight and a truncating\n                      <jats:italic>RFX6<\/jats:italic>\n                      mutation to highlight the severe metabolic instability that may occur in such patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0162_abs_002\">\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a preterm male infant born at 31\u00a0weeks of gestation with a birth weight of 880\u202fg who presented with duodenal atresia, severe hyperglycemia beginning on postnatal day 4, chronic diarrhea, pancreatic exocrine insufficiency, and cholestasis. Imaging revealed gallbladder aplasia and pancreatic hypoplasia. Genetic analysis identified a homozygous truncating variant in the\n                      <jats:italic>RFX6<\/jats:italic>\n                      gene (c.1573C&gt;T; p.Arg525Ter), confirming the diagnosis of MRS. Despite intensive supportive therapy, including insulin infusion, nutritional support, and management of pancreatic insufficiency, the patient developed persistent metabolic instability and progressive liver dysfunction and died on postnatal day\u00a0195.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0162_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case highlights MRS in an extremely low birth weight preterm infant and underscores the severe metabolic instability associated with truncating\n                      <jats:italic>RFX6<\/jats:italic>\n                      mutations. Early recognition and genetic diagnosis are essential for appropriate management and genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2026-0162","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T05:55:27Z","timestamp":1782194127000},"page":"933-938","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal diabetes due to a truncating RFX6 mutation in an extremely low birth weight preterm infant with Mitchell\u2013Riley syndrome"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-6580","authenticated-orcid":false,"given":"Birgul","family":"Mutlu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology , Bursa City Hospital , Bursa , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"2026100816572550209_j_jpem-2026-0162_ref_001","doi-asserted-by":"crossref","unstructured":"Mitchell, J, Punthakee, Z, Lo, B, Bernard, C, Chong, K, Newman, C, et al.. 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Eur J Med Genet 2016;59:429\u201335. https:\/\/doi.org\/10.1016\/j.ejmg.2016.08.005.","DOI":"10.1016\/j.ejmg.2016.08.005"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_004","doi-asserted-by":"crossref","unstructured":"Khan, N, Dandan, W, Al Hassani, N, Hadi, S. A newly discovered mutation in the RFX6 gene in Mitchell-Riley syndrome. J\u00a0Clin Res Pediatr Endocrinol 2016;8:246\u20139. https:\/\/doi.org\/10.4274\/jcrpe.2387.","DOI":"10.4274\/jcrpe.2387"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_005","doi-asserted-by":"crossref","unstructured":"Alruqaie, N, Alfadhel, M. Mitchell-Riley syndrome: report of a novel mutation and review of the literature. J\u00a0Biochem Clin Genet 2018;1:87\u201392. https:\/\/doi.org\/10.24911\/JBCG.183-1529491124.","DOI":"10.24911\/JBCGenetics\/183-1529491124"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_006","doi-asserted-by":"crossref","unstructured":"Concepcion, JP, Reh, CS, Daniels, M, Liu, X, Paz, VP, Ye, H, et al.. Neonatal diabetes, gallbladder agenesis, duodenal atresia and intestinal malrotation caused by a novel homozygous mutation in RFX6. Pediatr Diabetes 2014;15:67\u201372. https:\/\/doi.org\/10.1111\/pedi.12063.","DOI":"10.1111\/pedi.12063"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_007","doi-asserted-by":"crossref","unstructured":"Kambal, MA, Al-Harbi, DA, Al-Sunaid, AR, Al-Atawi, MS. Mitchell-Riley\u00a0syndrome due to a novel mutation in RFX6. Front Pediatr 2019;7:243. https:\/\/doi.org\/10.3389\/fped.2019.00243.","DOI":"10.3389\/fped.2019.00243"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_008","doi-asserted-by":"crossref","unstructured":"Passone, CGB, Vermillac, G, Staels, W, Besancon, A, Kariyawasam, D, Godot, C, et al.. Mitchell-Riley syndrome: improving clinical outcomes and searching for functional impact of RFX6 mutations. Front Endocrinol (Lausanne) 2022;13:802351. https:\/\/doi.org\/10.3389\/fendo.2022.802351.","DOI":"10.3389\/fendo.2022.802351"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_009","doi-asserted-by":"crossref","unstructured":"Sadhu, S, Albitar, N, AlKhouly, M, Farooque, A. Mitchell-Riley syndrome: a rare genetic disorder. Rare 2024;2:100042. https:\/\/doi.org\/10.1016\/j.rare.2024.100042.","DOI":"10.1016\/j.rare.2024.100042"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_010","doi-asserted-by":"crossref","unstructured":"Sansbury, FH, Kirel, B, Caswell, R, Allen, HL, Flanagan, SE, Hattersley, AT, et al.. Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus. Eur J Hum Genet 2015;23:1744\u20138. https:\/\/doi.org\/10.1038\/ejhg.2015.161.","DOI":"10.1038\/ejhg.2015.161"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_011","doi-asserted-by":"crossref","unstructured":"Adamkin, DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011;127:575\u20139. https:\/\/doi.org\/10.1542\/peds.2010-3851.","DOI":"10.1542\/peds.2010-3851"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_012","doi-asserted-by":"crossref","unstructured":"Thornton, PS, Stanley, CA, De Leon, DD, Harris, D, Haymond, MW, Hussain, K, et al.. Recommendations from the pediatric endocrine society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J\u00a0Pediatr 2015;167:238\u201345. https:\/\/doi.org\/10.1016\/j.jpeds.2015.03.057.","DOI":"10.1016\/j.jpeds.2015.03.057"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_013","doi-asserted-by":"crossref","unstructured":"Golshan-Tafti, M, Dastgheib, SA, Bahrami, R, Yeganegi, M, Aghasipour, M, Marzbanrad, Z, et al.. Genetic underpinnings of neonatal diabetes: a review of current research. Egypt J Med Hum Genet 2024;25:119. https:\/\/doi.org\/10.1186\/s43042-024-00594-3.","DOI":"10.1186\/s43042-024-00594-3"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_014","doi-asserted-by":"crossref","unstructured":"Kocova, M. Genetic spectrum of neonatal diabetes. Balk J Med Genet 2021;23:5\u201315. https:\/\/doi.org\/10.2478\/bjmg-2020-0027.","DOI":"10.2478\/bjmg-2020-0027"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_015","doi-asserted-by":"crossref","unstructured":"Kumarasiri, IM, Hoole, TJ, Nimanthi, MWA, Jayasundara, I, Balasubramaniam, R, Atapattu, N. Clinical and genetic characteristics and outcome in patients with neonatal diabetes mellitus from a low-middle income country. J\u00a0Clin Res Pediatr Endocrinol 2024;16:507\u201313. https:\/\/doi.org\/10.4274\/jcrpe.galenos.2024.","DOI":"10.4274\/jcrpe.galenos.2024.2024-2-17"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_016","doi-asserted-by":"crossref","unstructured":"Gobble, MRS, Stone, SI. Neonatal and syndromic forms of diabetes. Curr Diab Rep 2025;25:26. https:\/\/doi.org\/10.1007\/s11892-024-01567-x.","DOI":"10.1007\/s11892-024-01567-x"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_017","doi-asserted-by":"crossref","unstructured":"Trott, J, Alpagu, Y, Tan, EK, Shboul, M, Dawood, Y, Elsy, M, et al.. Mitchell-Riley syndrome iPSCs exhibit reduced pancreatic endoderm differentiation due to a mutation in RFX6. Development 2020;147:dev194878. https:\/\/doi.org\/10.1242\/dev.194878.","DOI":"10.1242\/dev.194878"},{"key":"2026100816572550209_j_jpem-2026-0162_ref_018","doi-asserted-by":"crossref","unstructured":"Amorim, MZ, Houghton, JAL, Carmo, S, Salva, I, Pita, A, Pereira-da-Silva, L. Mitchell\u2013Riley syndrome: a novel mutation in RFX6 gene. 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