Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy
Maturity-onset diabetes of the young (MODY) is a rare, genetically heterogeneous form of diabetes characterized by early-onset dysglycaemia, typically before 25 years of age, and autosomal dominant inheritance. Among the different forms of MODY, HNF4A-MODY (MODY1) is caused by mutations in the HNF4A...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1590935/full |
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| author | Chiara Gulisano Concetta Aloi Alessandro Salina Camilla Marazzi Giordano Spacco Serena Cappato Renata Bocciardi Renata Bocciardi Dario Iafusco Giacomo Tantari Giuseppe d'Annunzio Nicola Minuto Mohamad Maghnie Marta Bassi Francesca Faravelli |
| author_facet | Chiara Gulisano Concetta Aloi Alessandro Salina Camilla Marazzi Giordano Spacco Serena Cappato Renata Bocciardi Renata Bocciardi Dario Iafusco Giacomo Tantari Giuseppe d'Annunzio Nicola Minuto Mohamad Maghnie Marta Bassi Francesca Faravelli |
| author_sort | Chiara Gulisano |
| collection | DOAJ |
| description | Maturity-onset diabetes of the young (MODY) is a rare, genetically heterogeneous form of diabetes characterized by early-onset dysglycaemia, typically before 25 years of age, and autosomal dominant inheritance. Among the different forms of MODY, HNF4A-MODY (MODY1) is caused by mutations in the HNF4A gene, which encodes a transcription factor essential for glucose metabolism. Here, we describe a novel splicing variant in the HNF4A gene (c.319+1G>A) identified in a 15-year-old girl with non-ketoacidotic diabetes and a family history of diabetes. Initially diagnosed with Type 1 diabetes (T1D), she required low insulin doses and displayed negative autoimmune markers. Genetic testing revealed the heterozygous variant inherited from her father and functional studies confirmed the variant's impact on splicing. Following the diagnosis of HNF4A-MODY, the patient's treatment was switched from insulin to sulfonylureas, resulting in improved glycaemic control and time in range, along with an improved quality of life. The report highlights the importance of considering MODY in young patients with diabetes who lack typical T1D characteristics and the value of combining clinical, genetic, and functional testing for accurate diagnosis and personalized treatment. |
| format | Article |
| id | doaj-art-0b1121528c99416fbe0d5641e00dfaad |
| institution | OA Journals |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-0b1121528c99416fbe0d5641e00dfaad2025-08-20T01:52:59ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-05-011210.3389/fmed.2025.15909351590935Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapyChiara Gulisano0Concetta Aloi1Alessandro Salina2Camilla Marazzi3Giordano Spacco4Serena Cappato5Renata Bocciardi6Renata Bocciardi7Dario Iafusco8Giacomo Tantari9Giuseppe d'Annunzio10Nicola Minuto11Mohamad Maghnie12Marta Bassi13Francesca Faravelli14Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyLabsiem, Pediatric Clinic, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, ItalyLabsiem, Pediatric Clinic, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genoa, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyMedical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyMedical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyRegional Center for Pediatric Diabetes, Department of Pediatrics, University of the Study of Campania, Naples, ItalyPediatric Clinic, IRCCS Istituto Giannina Gaslini, Genoa, ItalyPediatric Clinic, IRCCS Istituto Giannina Gaslini, Genoa, ItalyPediatric Clinic, IRCCS Istituto Giannina Gaslini, Genoa, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyDepartment of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, ItalyGenomics and Clinical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genoa, ItalyMaturity-onset diabetes of the young (MODY) is a rare, genetically heterogeneous form of diabetes characterized by early-onset dysglycaemia, typically before 25 years of age, and autosomal dominant inheritance. Among the different forms of MODY, HNF4A-MODY (MODY1) is caused by mutations in the HNF4A gene, which encodes a transcription factor essential for glucose metabolism. Here, we describe a novel splicing variant in the HNF4A gene (c.319+1G>A) identified in a 15-year-old girl with non-ketoacidotic diabetes and a family history of diabetes. Initially diagnosed with Type 1 diabetes (T1D), she required low insulin doses and displayed negative autoimmune markers. Genetic testing revealed the heterozygous variant inherited from her father and functional studies confirmed the variant's impact on splicing. Following the diagnosis of HNF4A-MODY, the patient's treatment was switched from insulin to sulfonylureas, resulting in improved glycaemic control and time in range, along with an improved quality of life. The report highlights the importance of considering MODY in young patients with diabetes who lack typical T1D characteristics and the value of combining clinical, genetic, and functional testing for accurate diagnosis and personalized treatment.https://www.frontiersin.org/articles/10.3389/fmed.2025.1590935/fullMODYHNF4A-MODYMODY1diabetes mellituscontinuous glucose monitoring (CGM)sulfonylureas |
| spellingShingle | Chiara Gulisano Concetta Aloi Alessandro Salina Camilla Marazzi Giordano Spacco Serena Cappato Renata Bocciardi Renata Bocciardi Dario Iafusco Giacomo Tantari Giuseppe d'Annunzio Nicola Minuto Mohamad Maghnie Marta Bassi Francesca Faravelli Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy Frontiers in Medicine MODY HNF4A-MODY MODY1 diabetes mellitus continuous glucose monitoring (CGM) sulfonylureas |
| title | Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy |
| title_full | Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy |
| title_fullStr | Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy |
| title_full_unstemmed | Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy |
| title_short | Case Report: Beyond type 1 diabetes: a case of delayed MODY1 diagnosis and successful transition to sulfonylurea therapy |
| title_sort | case report beyond type 1 diabetes a case of delayed mody1 diagnosis and successful transition to sulfonylurea therapy |
| topic | MODY HNF4A-MODY MODY1 diabetes mellitus continuous glucose monitoring (CGM) sulfonylureas |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1590935/full |
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