Biallelic Pathogenic Variants in IL2RA Cause Neonatal-Onset Monogenic Autoimmune Diabetes

Area of Science:

• Genetics
• Immunology
• Endocrinology

Background:

• Neonatal diabetes mellitus (NDM) is a rare condition often caused by genetic factors.
• Autoimmune diabetes can present in early childhood, sometimes associated with immune dysregulation.
• The Interleukin-2 Receptor Alpha (IL2RA) gene plays a critical role in immune system function.

Purpose of the Study:

• To describe new cases of early-onset diabetes linked to IL2RA.
• To highlight the autoimmune etiology of diabetes in these patients.
• To recommend IL2RA in genetic testing for specific pediatric diabetes cases.

Main Methods:

• Clinical case reporting of five new patients.
• Genetic analysis to identify biallelic pathogenic variants in IL2RA.
• Review of clinical presentation, including diabetes markers and immune status.

Main Results:

• Five new cases of neonatal/early childhood-onset diabetes due to IL2RA variants were identified.
• Autoimmune diabetes was the primary presentation in most cases (64%).
• Patients exhibited diabetic ketoacidosis, low C-peptide, and GAD antibody positivity, indicating autoimmune diabetes.

Conclusions:

• Biallelic pathogenic IL2RA variants are a significant cause of autoimmune neonatal diabetes.
• IL2RA should be a target in genetic testing for neonatal diabetes.
• Consider IL2RA testing in children with diabetes and concurrent immune dysregulation.