Neonatal diabetes mellitus around the world: Update 2024

Area of Science:

• Genetics
• Endocrinology
• Pediatrics

Background:

• Neonatal diabetes mellitus (NDM) is a rare, monogenic form of diabetes presenting within the first six months of life.
• The genetic landscape of NDM has expanded significantly since its initial discovery in the late 1990s.
• Ongoing research continues to identify novel genetic causes and refine understanding of NDM pathophysiology.

Purpose of the Study:

• To provide a comprehensive overview of recent advancements in neonatal diabetes mellitus research.
• To highlight the expanding list of NDM-associated genes and their implications.
• To discuss the diverse disease mechanisms and evolving therapeutic strategies for NDM.

Main Methods:

• Genetic sequencing and mutation analysis to identify NDM-causing genes.
• Utilizing advanced stem cell technologies, including induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs).
• Employing genome editing techniques like CRISPR for functional studies of NDM genes.

Main Results:

• Between 2018 and early 2024, six new NDM genes were discovered (CNOT1, FICD, ONECUT1, PDIA6, YIPF5, ZNF808).
• Three known disease-associated genes (EIF2B1, NARS2, KCNMA1) and three childhood diabetes genes (AGPAT2, BSCL2, PIK3R1) were also identified as NDM-related.
• The total number of identified NDM genes now exceeds 40, underscoring significant genetic heterogeneity.

Conclusions:

• The increasing number of NDM genes reveals diverse pathogenic mechanisms.
• State-of-the-art methodologies like iPSCs and CRISPR are crucial for investigating NDM.
• The genetic diversity necessitates tailored and varied therapeutic approaches for NDM patients.