Articles, Issue 3/2026, Брой 3/2026, Брой 3/2026, Articles
Diabetes of young onset (MODY) – a clinical caseand diagnostic and therapeutic approach
1 Clinic of Pediatric Endocrinology and Metabolic Diseases, Specialized Hospital for Active Treatment of Children’s Diseases “Prof. Ivan Mitev”, Sofia
2 Medical Center SARA, Sofia
3 Medical University – Sofia
4 Laboratory of Genomic Diagnostics, Sofia
Abstract
Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is often underdiagnosed and misclassified as type 1 or type 2 diabetes. MODY is characterized by beta-cell dysfunction, absence of autoantibodies, and a positive family history. In this report, we present a patient with a seven-year history of diabetes, unusually low daily insulin requirements, and negative pancreatic islet autoantibodies. Genetic testing revealed heterozygosity for the pathogenic variant c.598C>T (p.Arg200Trp) in exon 3 of the HNF1A gene, which is associated with MODY type 3.
Key words: monogenic diabetes, MODY 3, HNF1A
Bibliography
1. Libman I, Haynes A, Lyons S et al. ISPAD Clinical Practice Consensus Guidelines 2022: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2022;23:1160–74. doi:10.1111/pedi.13454
2. Hoffman LS, Fox TJ, Anastasopoulou C, et al. Maturity-onset diabetes in the young. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2026 Feb 7]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532900/
3. Greeley SAW, Polak M, Njølstad PR et al. ISPAD Clinical Practice Consensus Guidelines 2022: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2022;23:1188–211. doi:10.1111/pedi.13426
4. Tattersall RB. Mild familial diabetes with dominant inheritance. Q J Med. 1974;43:339–57
5. Shields BM, Hicks S, Shepherd MH et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010;53:2504–8. doi:10.1007/s00125-010-1799-4
6. Sharp LN, Colclough K, Murray Leech J et al. Population prevalence, penetrance, and mortality for genetically confirmed MODY. J Clin Endocrinol Metab. 2025;dgaf599. doi:10.1210/clinem/dgaf599
7. Todd JN, Kleinberger JW, Zhang H et al. Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration. Diabetes Care. 2021;44:2312–9. doi:10.2337/dc21-0491
8. Bellanné-Chantelot C, Carette C, Riveline JP et al. The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3. Diabetes. 2008;57:503–8. doi:10.2337/db07-0859
9. Chakera AJ, Steele AM, Gloyn AL et al. Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation. Diabetes Care. 2015;38:1383–92. doi:10.2337/dc14-2769
10. Константинова М, Савова Р, Аршинкова М. Моногенен диабет – особености, диагноза, диференциална диагноза и лечение. Неонатален диабет. GP News. 2010;7:5–8.
11. Савова Р, Славчева О. Моногенни форми на захарен диабет. Педиатрия Suppl За Общопрактикуващия Лекар. 13–21.
12. Mirshahi UL, Colclough K, Wright CF et al. Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts. Am J Hum Genet. 2022;109:2018–28. doi:10.1016/j.ajhg.2022.09.014
13. Wenzlau JM, Hutton JC. Novel Diabetes Autoantibodies and Prediction of Type 1 Diabetes. Curr Diab Rep. 2013;13:608–15. doi:10.1007/s11892-013-0405-9
14. Leighton E, Sainsbury CA, Jones GC. A Practical Review of C-Peptide Testing in Diabetes. Diabetes Ther. 2017;8:475–87. doi:10.1007/s13300-017-0265-4
15. Pearson ER, Starkey BJ, Powell RJ et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. The Lancet. 2003;362:1275–81. doi:10.1016/S0140-6736(03)14571-0
16. American Diabetes Association Professional Practice Committee for Diabetes* et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49:S183–215. doi:10.2337/dc26-S009
17. Crowley MT, Ng N, Goulden E et al. Sulphonylurea efficacy and end‐organ outcomes in the management of HNF4A ‐ MODY. Diabet Med. 2025;42:e70139. doi:10.1111/dme.70139
18. Wu HX, Chu TY, Iqbal J et al. Response to Letter to the Editor From Hooper: “Cardio-cerebrovascular Outcomes in MODY, Type 1 Diabetes, and Type 2 Diabetes: A Prospective Cohort Study.” J Clin Endocrinol Metab. 2024;109:e1416–7. doi:10.1210/clinem/dgad720
19. Steele AM, Shields BM, Wensley KJ et al. Prevalence of Vascular Complications Among Patients With Glucokinase Mutations and Prolonged, Mild Hyperglycemia. JAMA. 2014;311:279. doi:10.1001/jama.2013.283980
Address for correspondence:
Todor Ruskov
Clinic of Pediatric Endocrinology and Metabolic Diseases, SBAL “Prof. Ivan Mitev” –
Sofia
Blvd. “Acad. Ivan Evstatiev Geshov”, 11
1606, Sofia
e-mail: todor.e.ruskov@gmail.com