A family pedigree with ABCC8 gene mutation causing MODY12 with adolescent onset: A case report and literature review

Background　Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes mellitus (DM). MODY12 is a rare subtype, with few cases reported in China to date.Objective　To explore the clinical characteristics of MODY12, so as to enhance the understanding and management of this condition.Methods　A retrospective analysis was conducted on the clinical data about a patient with MODY12 caused by mutation in the ATP-binding cassette subfamily C member 8 (ABCC8) gene, supplemented by literature review.Results　The patient was a 32-year-old female with a BMI of 22.06 kg/m². She was hospitalized due to pancreatitis, during which examinations revealed a fasting blood glucose level of 11.99 mmol/L, a random blood glucose level of 21.07 mmol/L, and a glycated hemoglobin (HbA1c) level of 9.3%. Her fasting insulin was 15.112 μU/mL, with a peak postprandial insulin level of 55.747 μU/mL. The fasting C-peptide was 0.49 ng/mL, and the peak postprandial C-peptide was 3.04 ng/mL. All diabetes-related autoantibodies were negative, leading to a suspicion of a special type of diabetes. Whole-exome sequencing of the patient's familial genomic DNA, verified by Sanger sequencing in relatives, revealed that both the patient and her father carried a heterozygous ABCC8 (NM_000352.6) c.824G>A (p. Arg275Gln) mutation. Multiple bioinformatics tools predicted this variant to be pathogenic. Initially treated with basal insulin combined with miglitol, the patient was switched to low-dose sulfonylurea (glimepiride 1 mg/day) after genetic confirmation, achieving optimal glycemic control during follow-up. Conclusion　For young- or middle-aged-onset diabetes patients with negative autoantibodies, preserved pancreatic function, and no significant insulin resistance, MODY should be considered. For confirmed MODY12 cases with genetic testing, low-dose sulfonylurea therapy can achieve excellent glycemic control while avoiding unnecessary long-term insulin injections.