{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T19:02:21Z","timestamp":1774551741959,"version":"3.50.1"},"reference-count":22,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Summary<\/jats:title>\n \n RFX6<\/jats:italic>\n maturity-onset diabetes of the young (\n RFX6<\/jats:italic>\n -MODY) is a relatively new MODY subtype, with limited guidance on management, particularly in pregnancy. We report the clinical features and management of two female patients with\n RFX6<\/jats:italic>\n -MODY and their progression during and post-pregnancy. These patients were diagnosed with type 2 diabetes mellitus (DM) at ages 13 and 19 years, initially managed on dietary modification alone. They were subsequently diagnosed with\n RFX6<\/jats:italic>\n -MODY during pregnancy following calculation of MODY probability. Both required insulin during pregnancy and delivered healthy babies at 38 weeks. Three months post-delivery, tirzepatide was started for one of our patients and she has shown significant glycaemic improvement and weight loss. To our knowledge, this is the first reported use of tirzepatide in\n RFX6<\/jats:italic>\n -MODY.\n <\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n \n \n \n RFX6<\/jats:italic>\n -MODY may present at a much earlier age than previously reported in the literature.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Many patients with\n RFX6<\/jats:italic>\n -MODY do not appear to require insulin at diagnosis.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Tirzepatide may be a beneficial therapeutic option for managing patients with\n RFX6<\/jats:italic>\n -MODY who have adequate \u03b2-cell function.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Pregnancy management in patients with\n RFX6<\/jats:italic>\n -MODY is similar to type 2 DM, although higher insulin doses may be required.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-25-0142","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T15:46:50Z","timestamp":1769096810000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["RFX6 maturity-onset diabetes of the young: clinical considerations and novel use of tirzepatide"],"prefix":"10.1530","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8570-5012","authenticated-orcid":true,"given":"Prethivan Pillai","family":"Gopalakrishnan","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael","family":"Milne","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven John","family":"McNulty","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumudu","family":"Bujawansa","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram Prakash","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, St Helens Hospital, Prescot, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"416","reference":[{"key":"bib1","series-title":"J Clin Endocrinol Metab","first-page":"In press","article-title":"Population prevalence, penetrance, and mortality for genetically confirmed MODY","author":"Sharp LN","year":"2025","unstructured":"Sharp LN\n, \nColclough K\n, \nMurray Leech J\n, et al\n. Population prevalence, penetrance, and mortality for genetically confirmed MODY. J Clin Endocrinol Metab 2025 In press dgaf599. (https:\/\/doi.org\/10.1210\/clinem\/dgaf599)"},{"key":"bib2","series-title":"Pharmacogenomics J","first-page":"49","article-title":"Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes","volume":"15","author":"Artuso R","year":"2015","unstructured":"Artuso R\n, \nProvenzano A\n, \nMazzinghi B\n, et al.\n Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes. Pharmacogenomics J 2015 15 49\u201354. (https:\/\/doi.org\/10.1038\/tpj.2014.37)"},{"key":"bib3","series-title":"Diabetologia","first-page":"1642","article-title":"RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function","volume":"67","author":"Ibrahim H","year":"2024","unstructured":"Ibrahim H\n, \nBalboa D\n, \nSaarim\u00e4ki-Vire J\n, et al.\n \nRFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function. Diabetologia 2024 67 1642\u20131662. (https:\/\/doi.org\/10.1007\/s00125-024-06163-y)"},{"key":"bib4","series-title":"J Biol Chem","first-page":"1929","article-title":"Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity","volume":"288","author":"Suzuki K","year":"2013","unstructured":"Suzuki K\n, \nHarada N\n, \nYamane S\n, et al.\n Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity. J Biol Chem 2013 288 1929\u20131938. (https:\/\/doi.org\/10.1074\/jbc.M112.423137)"},{"key":"bib5","series-title":"Nat Commun","first-page":"888","article-title":"Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance","volume":"8","author":"Patel KA","year":"2017","unstructured":"Patel KA\n, \nKettunen J\n, \nLaakso M\n, et al.\n Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance. Nat Commun 2017 8 888. (https:\/\/doi.org\/10.1038\/s41467-017-00895-9)"},{"key":"bib6","series-title":"Diabet Med","first-page":"1772","article-title":"A heterozygous protein-truncating 6 variant in a family with childhood-onset, pregnancy-associated and adult-onset diabetes","volume":"37","author":"Akiba K","year":"2020","unstructured":"Akiba K\n, \nUshijima K\n, \nFukami M\n, et al.\n A heterozygous protein-truncating 6 variant in a family with childhood-onset, pregnancy-associated and adult-onset diabetes. Diabet Med 2020 37 1772\u20131776. (https:\/\/doi.org\/10.1111\/dme.13970)"},{"key":"bib7","series-title":"J Diabetes Investig","first-page":"1914","article-title":"A novel RFX6 heterozygous mutation (p.R652X) in maturity-onset diabetes mellitus: a case report","volume":"12","author":"Imaki S","year":"2021","unstructured":"Imaki S\n, \nIizuka K\n, \nHorikawa Y\n, et al.\n A novel RFX6 heterozygous mutation (p.R652X) in maturity-onset diabetes mellitus: a case report. J Diabetes Investig 2021 12 1914\u20131918. (https:\/\/doi.org\/10.1111\/jdi.13545)"},{"key":"bib8","series-title":"AME Case Rep","first-page":"84","article-title":"RFX6 heterozygous frame-shift variation causes maturity-onset diabetes mellitus of the young (MODY) with refractory hyperlipidemia: a case report","volume":"9","author":"Li M","year":"2025","unstructured":"Li M\n, \nWang L\n, \nXing Y\n, et al.\n RFX6 heterozygous frame-shift variation causes maturity-onset diabetes mellitus of the young (MODY) with refractory hyperlipidemia: a case report. AME Case Rep 2025 9 84. (https:\/\/doi.org\/10.21037\/acr-24-266)"},{"key":"bib9","series-title":"Diabetes","first-page":"448","article-title":"RFX6 maintains gene expression and function of adult human islet \u03b1-cells","volume":"73","author":"Coykendall VMN","year":"2024","unstructured":"Coykendall VMN\n, \nQian MF\n, \nTellez K\n, et al.\n RFX6 maintains gene expression and function of adult human islet \u03b1-cells. Diabetes 2024 73 448\u2013460. (https:\/\/doi.org\/10.2337\/db23-0483)"},{"key":"bib10","series-title":"J Diabetes Res","article-title":"Serum glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in association with the risk of gestational diabetes: a prospective case-control study","volume":"2020","author":"Mosavat M","year":"2020","unstructured":"Mosavat M\n, \nOmar SZ\n, \nJamalpour S\n, et al.\n Serum glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in association with the risk of gestational diabetes: a prospective case-control study. J Diabetes Res 2020 2020 9072492. (https:\/\/doi.org\/10.1155\/2020\/9072492)"},{"key":"bib11","series-title":"Diabetologia","first-page":"1265","article-title":"The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes","volume":"55","author":"Shields BM","year":"2012","unstructured":"Shields BM\n, \nMcDonald TJ\n, \nEllard S\n, et al.\n The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 2012 55 1265\u20131272. (https:\/\/doi.org\/10.1007\/s00125-011-2418-8)"},{"key":"bib1","series-title":"J Clin Endocrinol Metab","first-page":"In press","article-title":"Population prevalence, penetrance, and mortality for genetically confirmed MODY","author":"Sharp LN","year":"2025","unstructured":"Sharp LN\n, \nColclough K\n, \nMurray Leech J\n, et al\n. Population prevalence, penetrance, and mortality for genetically confirmed MODY. J Clin Endocrinol Metab 2025 In press dgaf599. (https:\/\/doi.org\/10.1210\/clinem\/dgaf599)"},{"key":"bib2","series-title":"Pharmacogenomics J","first-page":"49","article-title":"Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes","volume":"15","author":"Artuso R","year":"2015","unstructured":"Artuso R\n, \nProvenzano A\n, \nMazzinghi B\n, et al.\n Therapeutic implications of novel mutations of the RFX6 gene associated with early-onset diabetes. Pharmacogenomics J 2015 15 49\u201354. (https:\/\/doi.org\/10.1038\/tpj.2014.37)"},{"key":"bib3","series-title":"Diabetologia","first-page":"1642","article-title":"RFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function","volume":"67","author":"Ibrahim H","year":"2024","unstructured":"Ibrahim H\n, \nBalboa D\n, \nSaarim\u00e4ki-Vire J\n, et al.\n \nRFX6 haploinsufficiency predisposes to diabetes through impaired beta cell function. Diabetologia 2024 67 1642\u20131662. (https:\/\/doi.org\/10.1007\/s00125-024-06163-y)"},{"key":"bib4","series-title":"J Biol Chem","first-page":"1929","article-title":"Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity","volume":"288","author":"Suzuki K","year":"2013","unstructured":"Suzuki K\n, \nHarada N\n, \nYamane S\n, et al.\n Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity. J Biol Chem 2013 288 1929\u20131938. (https:\/\/doi.org\/10.1074\/jbc.M112.423137)"},{"key":"bib5","series-title":"Nat Commun","first-page":"888","article-title":"Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance","volume":"8","author":"Patel KA","year":"2017","unstructured":"Patel KA\n, \nKettunen J\n, \nLaakso M\n, et al.\n Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance. Nat Commun 2017 8 888. (https:\/\/doi.org\/10.1038\/s41467-017-00895-9)"},{"key":"bib6","series-title":"Diabet Med","first-page":"1772","article-title":"A heterozygous protein-truncating 6 variant in a family with childhood-onset, pregnancy-associated and adult-onset diabetes","volume":"37","author":"Akiba K","year":"2020","unstructured":"Akiba K\n, \nUshijima K\n, \nFukami M\n, et al.\n A heterozygous protein-truncating 6 variant in a family with childhood-onset, pregnancy-associated and adult-onset diabetes. Diabet Med 2020 37 1772\u20131776. (https:\/\/doi.org\/10.1111\/dme.13970)"},{"key":"bib7","series-title":"J Diabetes Investig","first-page":"1914","article-title":"A novel RFX6 heterozygous mutation (p.R652X) in maturity-onset diabetes mellitus: a case report","volume":"12","author":"Imaki S","year":"2021","unstructured":"Imaki S\n, \nIizuka K\n, \nHorikawa Y\n, et al.\n A novel RFX6 heterozygous mutation (p.R652X) in maturity-onset diabetes mellitus: a case report. J Diabetes Investig 2021 12 1914\u20131918. (https:\/\/doi.org\/10.1111\/jdi.13545)"},{"key":"bib8","series-title":"AME Case Rep","first-page":"84","article-title":"RFX6 heterozygous frame-shift variation causes maturity-onset diabetes mellitus of the young (MODY) with refractory hyperlipidemia: a case report","volume":"9","author":"Li M","year":"2025","unstructured":"Li M\n, \nWang L\n, \nXing Y\n, et al.\n RFX6 heterozygous frame-shift variation causes maturity-onset diabetes mellitus of the young (MODY) with refractory hyperlipidemia: a case report. AME Case Rep 2025 9 84. (https:\/\/doi.org\/10.21037\/acr-24-266)"},{"key":"bib9","series-title":"Diabetes","first-page":"448","article-title":"RFX6 maintains gene expression and function of adult human islet \u03b1-cells","volume":"73","author":"Coykendall VMN","year":"2024","unstructured":"Coykendall VMN\n, \nQian MF\n, \nTellez K\n, et al.\n RFX6 maintains gene expression and function of adult human islet \u03b1-cells. Diabetes 2024 73 448\u2013460. (https:\/\/doi.org\/10.2337\/db23-0483)"},{"key":"bib10","series-title":"J Diabetes Res","article-title":"Serum glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in association with the risk of gestational diabetes: a prospective case-control study","volume":"2020","author":"Mosavat M","year":"2020","unstructured":"Mosavat M\n, \nOmar SZ\n, \nJamalpour S\n, et al.\n Serum glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in association with the risk of gestational diabetes: a prospective case-control study. J Diabetes Res 2020 2020 9072492. (https:\/\/doi.org\/10.1155\/2020\/9072492)"},{"key":"bib11","series-title":"Diabetologia","first-page":"1265","article-title":"The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes","volume":"55","author":"Shields BM","year":"2012","unstructured":"Shields BM\n, \nMcDonald TJ\n, \nEllard S\n, et al.\n The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 2012 55 1265\u20131272. (https:\/\/doi.org\/10.1007\/s00125-011-2418-8)"}],"container-title":["Endocrinology, Diabetes & Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2026\/1\/EDM-25-0142.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2026\/1\/EDM-25-0142.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2026\/1\/EDM-25-0142.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:20:24Z","timestamp":1774549224000},"score":1,"resource":{"primary":{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2026\/1\/EDM-25-0142.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":22,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/edm-25-0142","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}