Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions
Background: Neonatal diabetes (NDM) is a rare genetic disorder diagnosed in infants under six months of age, characterized by persistent hyperglycemia resulting from insufficient or absent insulin production. Unlike the more common forms of diabetes, such as type 1 diabetes (T1D) and type 2 diabetes...
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MDPI AG
2025-02-01
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| Series: | Children |
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| author | Michela Trada Chiara Novara Martina Moretto Edoardo Burzi Davide Tinti Luisa De Sanctis |
| author_facet | Michela Trada Chiara Novara Martina Moretto Edoardo Burzi Davide Tinti Luisa De Sanctis |
| author_sort | Michela Trada |
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| description | Background: Neonatal diabetes (NDM) is a rare genetic disorder diagnosed in infants under six months of age, characterized by persistent hyperglycemia resulting from insufficient or absent insulin production. Unlike the more common forms of diabetes, such as type 1 diabetes (T1D) and type 2 diabetes (T2D), NDM is predominantly caused by monogenic mutations affecting ATP-sensitive potassium (K-ATP) channels in pancreatic beta cells. The most common mutations involved in NDM are found in the KCNJ11 and ABCC8 genes, which encode the Kir6.2 and SUR1 subunits of the K-ATP channel, respectively. These mutations prevent normal insulin secretion by disrupting the function of the K-ATP channel. While genetic advances have identified about 40 genes implicated in NDM, the KCNJ11 and ABCC8 mutations are most commonly seen. Methods: This review provides a comprehensive exploration of the genetic basis, clinical presentation, and treatment strategies for NDM including the role of sulfonylureas, which have revolutionized the management of this condition. Furthermore, it presents a detailed case study of an infant diagnosed with an ABCC8 mutation, illustrating the pivotal role of genetic testing in guiding clinical decisions. Conclusions: Finally, the article discusses challenges in management, such as the persistence of neurological impairments, and outlines potential directions for future research including genetic therapies and prenatal diagnosis. |
| format | Article |
| id | doaj-art-d1ebbb77e4d04b9b95d608dacf19bdcd |
| institution | DOAJ |
| issn | 2227-9067 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj-art-d1ebbb77e4d04b9b95d608dacf19bdcd2025-08-20T02:44:42ZengMDPI AGChildren2227-90672025-02-0112221910.3390/children12020219Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future DirectionsMichela Trada0Chiara Novara1Martina Moretto2Edoardo Burzi3Davide Tinti4Luisa De Sanctis5Department of Pediatric Endocrinology, Regina Margherita Children’s Hospital, 10126 Torino, ItalyDepartment of Public Health and Pediatric Sciences, University of Torino, 10126 Torino, ItalyDepartment of Public Health and Pediatric Sciences, University of Torino, 10126 Torino, ItalyDepartment of Public Health and Pediatric Sciences, University of Torino, 10126 Torino, ItalyDepartment of Pediatric Endocrinology, Regina Margherita Children’s Hospital, 10126 Torino, ItalyDepartment of Pediatric Endocrinology, Regina Margherita Children’s Hospital, 10126 Torino, ItalyBackground: Neonatal diabetes (NDM) is a rare genetic disorder diagnosed in infants under six months of age, characterized by persistent hyperglycemia resulting from insufficient or absent insulin production. Unlike the more common forms of diabetes, such as type 1 diabetes (T1D) and type 2 diabetes (T2D), NDM is predominantly caused by monogenic mutations affecting ATP-sensitive potassium (K-ATP) channels in pancreatic beta cells. The most common mutations involved in NDM are found in the KCNJ11 and ABCC8 genes, which encode the Kir6.2 and SUR1 subunits of the K-ATP channel, respectively. These mutations prevent normal insulin secretion by disrupting the function of the K-ATP channel. While genetic advances have identified about 40 genes implicated in NDM, the KCNJ11 and ABCC8 mutations are most commonly seen. Methods: This review provides a comprehensive exploration of the genetic basis, clinical presentation, and treatment strategies for NDM including the role of sulfonylureas, which have revolutionized the management of this condition. Furthermore, it presents a detailed case study of an infant diagnosed with an ABCC8 mutation, illustrating the pivotal role of genetic testing in guiding clinical decisions. Conclusions: Finally, the article discusses challenges in management, such as the persistence of neurological impairments, and outlines potential directions for future research including genetic therapies and prenatal diagnosis.https://www.mdpi.com/2227-9067/12/2/219neonatal diabetesKCNJ11ABCC8sulfonylureasgenetic mutationsATP-sensitive potassium channels |
| spellingShingle | Michela Trada Chiara Novara Martina Moretto Edoardo Burzi Davide Tinti Luisa De Sanctis Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions Children neonatal diabetes KCNJ11 ABCC8 sulfonylureas genetic mutations ATP-sensitive potassium channels |
| title | Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions |
| title_full | Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions |
| title_fullStr | Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions |
| title_full_unstemmed | Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions |
| title_short | Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions |
| title_sort | diagnosis and treatment of neonatal diabetes caused by atp channel mutations genetic insights sulfonylurea therapy and future directions |
| topic | neonatal diabetes KCNJ11 ABCC8 sulfonylureas genetic mutations ATP-sensitive potassium channels |
| url | https://www.mdpi.com/2227-9067/12/2/219 |
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