SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Genetic Landscape of Neonatal Diabetes Mellitus (NDM) in the Middle East, North Africa, and Türkiye (MENAT): A Systematic Review
Salma Younes 1,2
Faisal Elmi Ibrahim 3
Ofelia Masoud 2
Sara Awwad 2
Halah Noor Nasir 2
Hatem Zayed 2
Nader Al-Dewik 3
1. Qatar University, Doha, Qatar
2. Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha, Qatar
3. Women’s Wellness and Research Center, Hamad Medical Corporation, Doha, Qatar
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Abstract
Background: Neonatal Diabetes Mellitus (NDM) is a rare, heterogeneous condition characterized by insulin-requiring hyperglycemia within the first six months of life. Although many NDM-associated genetic variants have been identified globally, the mutational spectrum and its relationship to phenotypic diversity within the Middle East, North Africa and Türkiye (MENAT) remain underexplored. Objective: To systematically review genetically confirmed variants reported in MENAT NDM and summarize genetic diversity and genotype-phenotype correlations. Methods: We performed a PRISMA-compliant search of PubMed, Scopus, Science Direct, Web of Science, and Google Scholar through July 2024. Studies of MENAT patients with pathogenic or likely pathogenic genetic variants in NDM were included. Data on genetic variants, clinical phenotypes, and treatment outcomes were extracted and synthesized. Results: Across 95 studies, we identified 195 variants in 23 genes, including 107 variants currently reported only in MENAT populations. EIF2AK3 accounted for largest proportion (22%), followed by KCNJ11 (11%) and ABCC8 (10%). Genotype-phenotype showed a broad spectrum of presentations, from isolated NDM to multisystem syndromes. Conclusion: MENAT NDM exhibits substantial genetic heterogeneity with clear diagnostic and therapeutic implications. Early genetic testing enables precision care, including potential sulfonylurea therapy in patients with K-ATP channel variants (KCNJ11/ABCC8), though treatment outcome reporting remains heterogeneous. Further studies are needed to interrogate the function of novel variants and elucidate disease mechanisms.
Summary
Keywords
neonatal diabetes, NDM, MENAT region, genetic diversity, genotype-phenotypecorrelation
Received
09 October 2024
Accepted
10 November 2025
Copyright
© 2025 Younes, Ibrahim, Masoud, Awwad, Nasir, Zayed and Al-Dewik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hatem Zayed; Nader Al-Dewik
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