Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy

Area of Science:

• Endocrinology
• Genetics
• Neonatal Medicine

Background:

• Transient neonatal diabetes mellitus (TNDM) is a rare condition with two primary genetic etiologies: activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or chromosome 6q24 abnormalities (6q24/TNDM).
• Understanding the distinct clinical presentations and treatment outcomes associated with these genetic causes is crucial for effective management.

Purpose of the Study:

• To compare the clinical features and treatment responses between patients with KATP/TNDM and 6q24/TNDM.
• To identify specific clinical indicators that may suggest one genetic etiology over the other.

Main Methods:

• Retrospective analysis of a dataset of Italian patients diagnosed with TNDM.
• Comparison of clinical features and treatment strategies in 22 KATP/TNDM patients and 12 6q24/TNDM patients.

Main Results:

• Patients with 6q24/TNDM exhibited earlier diabetes onset and lower birth weight compared to KATP/TNDM patients.
• Remission of diabetes was longer in KATP/TNDM patients (21.5 weeks) than in 6q24/TNDM patients (12 weeks).
• Sulfonylurea therapy demonstrated efficacy in inducing long-lasting remission, particularly in KATP/TNDM patients, including those with mutations previously associated with permanent neonatal diabetes.

Conclusions:

• Genetic analysis for KATP genes should be prioritized in suspected TNDM cases, unless macroglossia and/or umbilical hernia are present, suggesting 6q24 abnormalities.
• Diabetes remission without pharmacological intervention does not exclude the need for genetic testing.
• Early sulfonylurea treatment can lead to sustained diabetes remission in KATP-related TNDM, and adult patients with KATP/TNDM mutations respond well to sulfonylurea monotherapy.