Children With Diabetes and At Least One Non-Autoimmune Feature Should Be Considered for Monogenic Diabetes Testing

Area of Science:

• Pediatric Endocrinology
• Clinical Genetics
• Diabetes Research

Background:

• Current monogenic diabetes testing in children primarily focuses on Maturity Onset Diabetes in the Young (MODY) or known genetic syndromes.
• A broader diagnostic approach may be beneficial for children presenting with syndromic diabetes.

Purpose of the Study:

• To evaluate the utility of genetic testing for monogenic diabetes in all children with diabetes exhibiting at least one non-autoimmune extra-pancreatic feature.
• To determine if expanded genetic screening is warranted for this patient group.

Main Methods:

• Recruitment of 183 children with diabetes and at least one non-autoimmune extra-pancreatic feature.
• Measurement of islet-autoantibodies and type 1 diabetes genetic risk score (T1DGRS).
• Targeted next-generation sequencing to identify known monogenic diabetes causes.

Main Results:

• Monogenic diabetes was confirmed in 33% (61/183) of children.
• Recessive aetiologies were common (84%), with WFS1, SLC19A2, and SLC29A3 variants being most frequent.
• Higher parental consanguinity and multi-systemic features were observed in monogenic cases.
• Low T1DGRS and negative/untested antibodies increased the likelihood of monogenic diabetes.

Conclusions:

• Monogenic diabetes testing should be considered for children with diabetes and non-autoimmune extra-pancreatic features.
• Islet-autoantibody and T1DGRS measurements can effectively prioritize genetic testing in these children.