MON-219 Presentation of Glucokinase-Maturity-Onset Diabetes of the Young (GCK-MODY 2) in Obesity and with Transient Autoantibodies in Children and Adolescents

Abstract Disclosure: E. Volcotrub: None. F. Melean: None. M. Gangat: None. S.B. Ten: None. Introduction: MODY-2 is frequently misdiagnosed as diabetes type 1 or type 2. GCK-MODY 2 is caused by heterozygous inactivating mutations in the GCK gene. Treatment is not indicated. Aim: To evaluate the genetic background of 29 patients with diabetes, negative islet cell antibodies, normal C-peptide, and positive family history of diabetes. Methodology: Genetic testing was done in 29 patients using the Invitae monogenic diabetes panel of 28 genes. Results: GCK-MODY2 was identified in 7 (24%) cases from 29 positive MODY cases. The description of the cases is as followsFather and 2 sons of Asian descent carried heterozygous GCK gene, c.452C>A (p.Ser151Tyr), which was classified as likely pathogenic. The first son was diagnosed at 3.6 yrs old. of age with HbA1c of 6.4 & 6.6%. At 6.9 yrs of age, the BMI was 17. At 5 yrs of age the ZnT8Ab was mildly elevated, repeated every 6 months, and continued to be negative for the last 2 yrs. The second son was diagnosed at 5 yrs old. HbA1c was 6.6% and 6.7%. At 11.9 yrs of age, the BMI was normal at 17.3. Father at 31 yrs of age was diagnosed with diabetes with HbA1c of 6.6% and had a BMI of 25, in addition to GCK he had GLIS3 c.2251G>A, (p.Glu751Lys), VUS. He was initially treated with Metformin. His paternal grandfather and paternal brother also have diabetes.A 20-year-old Hispanic girl was diagnosed with diabetes at 14 yrs old. Hb A1c was 11%, and she had elevated TG, low HDL, and fatty liver. Her mother, maternal sister, and brother, MGM have diabetes. Her BMI was 35.4. She was found to have GCK c.1033C>G (p.Arg345Gly), VUS. She was treated with Glyburide, Metformin, Basaglar, and Victoza. When BMI improved to 31 her glucose level improved, her HbA1c came down to 8.0%, and only metformin was used for treatment. After she gained weight again BMI 36, was restarted on glyburide and Victoza.A 15-year-old Hispanic boy was diagnosed with diabetes, with a BMI of 16.7, and was found to have GCK variant c.379T>C (p.Ser127Pro), classified as VUS. HbA1c was stable between 6.3-6.5%. No treatment was necessary. The father has a history of diabetes.A 20-year-old Caucasian was diagnosed at 13 yrs old with a BMI of 33.4 and was found to have GCK, a pathogenic mutation. He had a HbA1c of 6-6.5%. His mother & brother have h/o diabetes.A 16-year-old Asian girl was diagnosed at 16 yrs, with a BMI of 21, HbA1c of 6.5%, had a GCK c.762T>A(p.Asn254Lys), classified as pathogenic. Father & PGF have diabetes. IA-2 autoantibodies were positive at 11 U/ml. She has been recently diagnosed, and the antibodies need to be rechecked. Conclusion: MODY diagnosis should be considered regardless of BMI. The presence of severe obesity in cases of GCK heterozygotes treatment with insulin sensitizers, insulin, and GLPs becomes necessary. After normalization of weight, no treatment is necessary except for weight control. In MODY-2 transient islet cell antibodies, ZnT8 can be observed and should not exclude MODY. Presentation: Monday, July 14, 2025