Endocrine Abstracts

JOINT3508

Introduction: Maturity-onset diabetes of the young type 10 (MODY 10) is a very rare monogenic form of diabetes caused by mutations in the insulin gene, leading to impaired insulin synthesis or secretion. This condition presents with early-onset hyperglycemia, often before age 25, and follows an autosomal dominant inheritance. MODY 10 requires precise genetic diagnosis and tailored management strategies.

Methods: We present the case of a 35-year-old patient diagnosed with MODY 10, followed-up in the Endocrinology Department of our hospital.

Results: The patient presented to the Emergency Department with nausea, vomiting and weight loss. Hyperglycemia was detected, leading to a diabetes diagnosis. The patient had a low body mass index of 18kg/m². His family history included a mother diagnosed with diabetes at the same age and requiring insulin therapy a decade later. Initial tests revealed a C-peptide level of 0. 8ng/mL, while autoantibodies (GAD, ICA, IA2 and insulin antibodies) were negative. Considering the family history and clinical presentation, MODY 3 was initially suspected, as it is the most common subtype. However, genetic testing was negative. He was treated with basal insulin, oral antidiabetic drugs, and later with fast-acting insulin. After several years without a clear diagnosis while maintaining a C-peptide of 1. 2ng/mL, a comprehensive genetic panel (next-generation sequencing) was performed. The results identified a heterozygous mutation in the insulin gene, c. 130G>A, p. (Gly44Arg), very rare in population databases (MAF gnomAD 0, 002%), confirming the diagnosis of MODY 10. The patient was than referred to genetic counselling and currently maintains good metabolic control on glargine insulin, metformin, dapagliflozin and sitagliptin, with an HbA1c of 6. 3% and maintaining partial pancreatic function (C-peptide 1. 14ng/mL).

Conclusion: Underweight MODY patients are often misdiagnosed as type 1 diabetes, particularly when C-peptide levels are low and insulin therapy is required at diagnosis. However, MODY diagnosis should be considered in the presence of family history, negative autoantibodies and C-peptide above 0. 6ng/mL, even with an atypical age of onset. This rare mutation underscores the importance of extensive genetic testing in atypical diabetes cases. Referral to genetic counselling is essential to identify affected family members.