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

Myers R., YILDIZ M., Nuri Ozbek M., Manzoor J., Ibrahim M., Yajnik C., ...Daha Fazla

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1210/clinem/dgaf430
  • Dergi Adı: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, Nature Index
  • Anahtar Kelimeler: diabetes, monogenic diabetes, pediatrics, syndromic diabetes, genetic testing
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Aims: Monogenic diabetes testing in children currently targets Maturity Onset Diabetes in the Young (MODY) or recognised genetic syndromes. Objective: We aim to determine whether genetic testing for monogenic diabetes should be performed for all children with diabetes and at least one non-autoimmune extra-pancreatic feature (syndromic diabetes). Methods: We recruited 183 children with diabetes and at least one non-autoimmune extra-pancreatic feature (50% (n=91) with self-reported consanguinity). We measured islet-autoantibodies and type 1 diabetes genetic risk score (T1DGRS) and used targeted next generation sequencing to analyse all known causes of monogenic diabetes. Results: 33% (61/183) of children had confirmed monogenic diabetes. Of these, 84% (51/61) had recessive aetiologies with variants in WFS1 (46%), SLC19A2 (12%) and SLC29A3 (12%) being most common. Monogenic cases compared to non-monogenic had similar age of diagnosis (7.4 vs 6, p=0.1) and BMI z-score (-0.08 vs -0.41, p=0.3) but had higher parental consanguinity (62% vs 19%, p=0.01) and features in multiple organ systems (53% vs 28%, p=0.01). Only 59% reported well recognised features of their associated genetic syndrome. Children with low T1DGRS (<50th centile of T1D population) and negative/untested antibodies were more likely to have monogenic cause compared to positive antibodies or negative/untested antibodies and a high T1DGRS (>= 50th centile) (48% vs 3% vs 7%, p<0.0001). Conclusion: Children with diabetes and at least one non-autoimmune extra-pancreatic feature should be considered for monogenic diabetes testing. Measurement of islet-autoantibodies and T1DGRS help prioritise genetic testing.