Endocrine Abstracts

JOINT3804

Introduction: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that results from genetic defects that lead to β-cell dysfunction. Due to the heterogeneity of its clinical features and the lack of a single diagnostic criterion, MODY can often be misdiagnosed as type 1 or type 2 diabetes, and therefore its diagnosis is mostly based on genetic testing. Correct diagnosis of monogenic diabetes can significantly change treatment. This study aimed to evaluate the relationship between the clinical features of the cases and the detected genetic variations and to examine the effect of early diagnosis on diabetes management.

Material and Methods: The results of patients who were followed up in Tekirdağ Dr.İsmail Fehmi Cumalıoğlu City Hospital, Department of Pediatric Endocrinology between August 2023-December 2024 and studied the gene panel associated with monogenic diabetes were evaluated. Genetic analysis was performed using the Next Generation Sequencing Analysis (NGS). Variants classified according to the ACMG 2015 Guideline criteria were retrospectively examined.

Results: Mutations were detected in 11/16 (68%) cases that underwent genetic analysis with a preliminary diagnosis of MODY. Among the cases in which mutations were detected; heterozygous mutations were detected in the GCK genes(5/11), HNF1A(3/11), ABCC8(2/11) and G6PC2(1/11). The cases in which GCK mutations were detected applied with a complaint of coincidental hyperglycemia and were followed only with diet and lifestyle changes. Cases 1 and 2 with HNF1A mutations were female twins (15.4 years old) and applied with hyperglycemia. Case 3 (HNF1A mutation) was male (16.3 years old) and applied with diabetes symptoms. Diabetes antibodies were negative. Hba1c values of the cases at the time of application were 9.4%-11%-12%, respectively. Subcutaneous insulin treatment was started. In the genetic analysis of the patients, heterozygous c.685C>T (p.Arg229*) (in twin cases) and c.391C>T (p.Arg131Trp) (case 3) variants were detected. The cases were switched to oral sulfonylurea (gliclazide) and subcutaneous insulin treatments were stopped. One of the cases with mutation detected in the ABCC8 gene presented with diabetic ketosis and insulin treatment was continued.

Conclusion: Based on these clinical cases, the importance of early recognition and awareness of the signs and symptoms of MODY has been emphasized. In clinical practice, strict screening criteria should be established to balance cost-effectiveness and identification. The results of diabetes autoantibodies, family history of diabetes, age at onset, and endogenous insulin secretion should be taken into account to determine whether genetic testing is necessary. When suspicion arises, genetic testing should be performed to diagnose MODY and ensure early treatment and accurate family screening.