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

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

  • By

  • Rebecca Myers

  • Melek Yildiz

  • Mehmet Nuri Ozbek

  • Jaida Manzoor

  • Mohsina Ibrahim

  • Chittaranjan Yajnik

  • Muge Atar

  • Zeynep Şiklar

  • Sezer Acar

  • Evgenia Globa

  • Omneya Magdy Omar

  • Huseyin Demirbilek

  • Samar Hassan

  • Korcan Demir

  • Misbah Hanif

  • Tulay Guran

  • Nihal Hatipoglu

  • Cemil Koçyiğit

  • Kevin Colclough

  • Jayne Houghton

  • Andrew Hattersley

  • Rachel Van Heugten

  • Kashyap Patel

  • Monogenic Diabetes Consortium

  • Y Abdelmeguid

  • S Abourazzak

  • A Annamalai

  • E Bhowmik

  • G Catli

  • S Chapman

  • H Eideh

  • V Jain

  • T Kontbay

  • V Mulliqi Kotori

  • G Supriya

  • S Musa

  • M Šandrk Beslać

  • M Sharaf

  • J Yong

  • G Yesiltepe Mutlu

  • R Yildirim

  • O Yilmaz

  • M Berberoglu

  • T Akcay

  • C Datar

  • S Dhadge

  • K Jog

  • August 1, 2025

  • 0 min

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Monogenic Diabetes Testing in Children with Diabetes and Non-Autoimmune Features

Overview

In a cohort of 183 pediatric patients with diabetes and at least one non-autoimmune extra-pancreatic feature, 33% were diagnosed with monogenic diabetes. Most monogenic cases had recessive etiologies, with WFS1, SLC19A2, and SLC29A3 variants being the most common. Islet-autoantibody testing and type 1 diabetes genetic risk scores (T1DGRS) helped prioritize genetic testing.

Background

Monogenic diabetes can present as isolated diabetes or as part of syndromic forms with extra-pancreatic features. Accurate diagnosis is critical for targeted treatment, prognosis, and management of associated complications. However, monogenic diabetes syndromes are often underdiagnosed, especially recessive forms prevalent in consanguineous populations. This study evaluates whether all children with diabetes and at least one non-autoimmune extra-pancreatic feature should undergo comprehensive genetic testing.

Data Highlights

CharacteristicMonogenic Diabetes (n=61)Non-Monogenic Diabetes (n=122)P-value
Age at Diagnosis (years)7.460.1
BMI z-score-0.08-0.410.3
Parental Consanguinity (%)62%19%0.01
Multiple Organ Systems Involved (%)53%28%0.01
Monogenic Diabetes Prevalence33% (61/183)
Common Genes in Monogenic CasesWFS1 (46%), SLC19A2 (12%), SLC29A3 (12%)
Monogenic Diagnosis by T1DGRS and AutoantibodiesLow T1DGRS & Negative/Untested Antibodies: 48% monogenic; Positive Antibodies: 3%; High T1DGRS & Negative/Untested Antibodies: 7% (P < 0.0001)

Key Findings

  • 33% of children with diabetes and at least one non-autoimmune extra-pancreatic feature had monogenic diabetes confirmed by genetic testing.
  • 84% of monogenic cases were recessive, with WFS1, SLC19A2, and SLC29A3 being the most frequent gene variants.
  • Monogenic and non-monogenic groups had similar age of onset and BMI z-scores, but monogenic cases had significantly higher parental consanguinity and multi-organ involvement.
  • Only 59% of monogenic cases exhibited well-recognized features of their associated syndromes, indicating phenotypic variability.
  • Children with low T1D genetic risk scores and negative or untested islet-autoantibodies were more likely to have monogenic diabetes, supporting the use of these biomarkers to prioritize genetic testing.

Clinical Implications

Children presenting with diabetes and any non-autoimmune extra-pancreatic feature should be considered for monogenic diabetes genetic testing regardless of the severity or type of features. Measurement of islet-autoantibodies and calculation of T1D genetic risk scores can help clinicians prioritize patients for testing, improving diagnostic yield and enabling tailored management strategies.

Conclusion

Comprehensive genetic testing in pediatric diabetes patients with non-autoimmune extra-pancreatic features reveals a high prevalence of monogenic diabetes, predominantly recessive forms. Biomarkers such as islet-autoantibodies and T1DGRS enhance diagnostic precision and should be integrated into clinical evaluation.

References

  1. Evaluation of Monogenic Diabetes Testing in Pediatric Patients Exhibiting Diabetes Alongside a Non-Autoimmune Characteristic, 2024

Original Source(s)

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

  • by Rebecca Myers, Melek Yildiz, Mehmet Nuri Ozbek, Jaida Manzoor, Mohsina Ibrahim, Chittaranjan Yajnik, Muge Atar, Zeynep Şiklar, Sezer Acar, Evgenia Globa, Omneya Magdy Omar, Huseyin Demirbilek, Samar Hassan, Korcan Demir, Misbah Hanif, Tulay Guran, Nihal Hatipoglu, Cemil Koçyiğit, Kevin Colclough, Jayne Houghton, Andrew Hattersley, Rachel Van Heugten, Kashyap Patel, Monogenic Diabetes Consortium, Y Abdelmeguid, S Abourazzak, A Annamalai, E Bhowmik, G Catli, S Chapman, H Eideh, V Jain, T Kontbay, V Mulliqi Kotori, G Supriya, S Musa, M Šandrk Beslać, M Sharaf, J Yong, G Yesiltepe Mutlu, R Yildirim, O Yilmaz, M Berberoglu, T Akcay, C Datar, S Dhadge, K Jog

  • August 1, 2025

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