ABCC8-Related Monogenic Diabetes Presenting Like Type 1 Diabetes in an Adolescent

Area of Science:

• Endocrinology
• Genetics
• Diabetes Research

Background:

• Differentiating monogenic diabetes from type 1 (T1D) and type 2 (T2D) is challenging but clinically significant.
• Monogenic diabetes, often caused by single gene mutations, can present atypically, complicating diagnosis.
• This case highlights the importance of considering monogenic causes in diabetes diagnoses, even with initial T1D presentation.

Observation:

• A 35-year-old woman, diagnosed with T1D at 18, presented with severe hyperglycemia (blood glucose >500 mg/dL, HbA1C >14%).
• She had negative antibody testing, unmeasurable C-peptide initially, low insulin requirements, and later, persistent low C-peptide.
• A protective human leukocyte antigen (HLA) allele was noted, prompting genetic investigation.

Findings:

• Genetic testing identified a pathogenic mutation in the ATP-binding cassette transporter sub-family C member 8 (ABCC8) gene, confirming ABCC8-related monogenic diabetes.
• The patient was successfully transitioned from insulin therapy to sulfonylurea medication.
• This diagnosis underscores that severe hyperglycemia does not exclude monogenic diabetes, especially with atypical features.

Implications:

• Patients with suspected T1D and atypical features (e.g., negative autoantibodies, low insulin needs, C-peptide persistence) should be evaluated for monogenic diabetes via genetic testing.
• Accurate diagnosis of monogenic diabetes enables tailored treatment, such as sulfonylurea therapy, potentially improving outcomes.
• This case expands understanding of ABCC8-related monogenic diabetes presentation and diagnostic pathways.