Genetic Breakthrough: Researchers Identify Rare New Type of Neonatal Diabetes Linked to TMEM167A Gene

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December 28, 2025

An international consortium of scientists has identified a previously unknown form of neonatal diabetes, providing a vital breakthrough for families affected by rare metabolic and neurological conditions. By combining advanced DNA sequencing with cutting-edge stem cell research, researchers discovered that mutations in a single gene—TMEM167A—are responsible for a syndrome that causes babies to develop diabetes, epilepsy, and microcephaly (a condition where a baby’s head is significantly smaller than expected) shortly after birth.

The study, published in The Journal of Clinical Investigation, was led by the University of Exeter Medical School in the UK and the Université Libre de Bruxelles (ULB) in Belgium. The findings not only offer immediate answers for the families of affected children but also provide a “roadmap” for understanding how the body produces insulin, potentially impacting the lives of millions living with more common forms of diabetes.

Decoding the Genetic Blueprint of Infancy

While most people associate diabetes with lifestyle factors (Type 2) or childhood autoimmune responses (Type 1), neonatal diabetes occurs within the first six months of life. It is an extremely rare condition, affecting roughly one in 90,000 to 160,000 live births. In more than 85% of these cases, the culprit is a specific genetic mutation.

In this latest effort, researchers examined six children from around the world who shared a specific clinical profile: early-onset diabetes accompanied by neurological challenges. Using whole-exome sequencing, the team identified rare, recessive variants in the TMEM167A gene across all six patients.

“Finding the DNA changes that cause diabetes in babies gives us a unique way to find the genes that play key roles in making and secreting insulin,” said Dr. Elisa de Franco, a lead researcher at the University of Exeter. “This discovery allowed us to clarify the function of a little-known gene, showing how it plays a key role in insulin secretion.”

From Stem Cells to Secrets of the Pancreas

To understand why this genetic change causes disease, the team turned to “disease modeling” using stem cells. At the ULB Center for Diabetes Research, Professor Miriam Cnop and her colleagues used CRISPR gene-editing technology to “knock out” the TMEM167A gene in human stem cells. They then guided these cells to become pancreatic beta cells—the cells responsible for making insulin.

The results were striking. When the TMEM167A gene was disrupted:

Insulin secretion failed: The cells could no longer release insulin properly in response to glucose.
Cellular Stress: The disruption triggered an internal stress response within the cells.
Cell Death: Eventually, the stress became so severe that the insulin-producing cells died.

Interestingly, the study found that while this gene is essential for beta cells and neurons (brain cells), it appears to be dispensable for other parts of the body. This explains why the affected children suffer from both diabetes and neurological issues like epilepsy, but otherwise appear to have healthy organ function.

Expert Perspectives: Why Small Discoveries Matter

For the general public, the discovery of a disease affecting only a handful of people might seem niche. However, medical experts emphasize that rare diseases are often the “window” through which we understand human biology.

“Every time we identify a single gene responsible for diabetes, we gain a new piece of the puzzle regarding how the pancreas works,” says Dr. Aruna S. Khan, a pediatric endocrinologist not involved in the study. “This gene, TMEM167A, seems to be a gatekeeper for the cellular machinery that packages insulin. By studying this rare failure, we might find ways to support beta cell health in the 589 million people worldwide living with Type 1 and Type 2 diabetes.”

Professor Cnop echoed this sentiment, noting that the ability to grow patient-specific cells in a lab is a game-changer. “This is an extraordinary model for studying disease mechanisms and testing treatments without putting patients at risk,” she said.

Public Health Implications and Practical Insights

For parents and healthcare providers, the primary takeaway is the importance of genetic testing in early-onset conditions.

Early Diagnosis: If a child is diagnosed with diabetes before six months of age, genetic testing is the gold standard of care. Identifying the specific gene can sometimes lead to more effective, personalized treatments (such as switching from insulin injections to oral medications, though it is not yet clear if that applies to TMEM167A).
Family Planning: Since this specific mutation is recessive, parents who carry the gene have a 25% chance of passing it to their children. Genetic counseling can provide these families with essential information.
The Future of Treatment: While there is currently no cure for TMEM167A-related diabetes, the discovery allows scientists to begin screening for drugs that might alleviate the cellular stress and prevent beta cell death.

Limitations and Counterarguments

Despite the excitement, researchers urge caution. This study involved a very small sample size—only six children. Because the condition is so rare, it will take years of international data collection to determine if there are variations in how the disease progresses.

Furthermore, while the stem cell models are highly accurate, they are grown in a controlled laboratory environment. How the TMEM167A mutation interacts with the complex environment of a living human body—including the immune system and fluctuating hormone levels—requires further clinical observation.

A Global Effort

This discovery was a massive undertaking, involving researchers from the UK, Belgium, Turkey, Egypt, and the United States. It was supported by major organizations, including Diabetes UK, the European Foundation for the Study of Diabetes, and the Novo Nordisk Foundation.

As the global medical community continues to map the human genome, the transition from “unknown illness” to “diagnosable condition” is becoming faster. For the six families involved in this study, the research provides more than just a name for a disease; it provides the hope that, through science, their children’s conditions may one day be treatable.

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.