Scientists Discover a Hidden Form of Diabetes in Newborns

Using state-of-the-art DNA sequencing and an advanced stem cell research model, an international group of scientists has identified a previously unknown form of diabetes that affects babies. The discovery sheds new light on how insulin-producing cells can fail early in life. The research was conducted by the University of Exeter Medical School in collaboration with the Université Libre de Bruxelles (ULB) in Belgium and other international partners. Together, the team found that mutations in a gene called TMEM167A are responsible for this rare form of neonatal diabetes.

Genetic Clues to Early-Onset Diabetes

Some infants develop diabetes within the first six months of life. This form is called neonatal diabetes and is fundamentally different from the well-known type 1 or type 2 diabetes. Neonatal diabetes is very rare, but medically significant because in most cases it has a genetic cause. In fact, studies show that over 85% of diabetes cases that occur before the age of 6 months are caused by inherited or newly developed changes in DNA. This means that the immune system does not usually attack the insulin-producing cells, as is the case with classic type 1 diabetes. Instead, there is a defect in the development or function of the insulin-producing beta cells in the pancreas.

In the new study, the researchers examined six children who not only had diabetes but also neurological disorders such as epilepsy and microcephaly. Microcephaly is a neurological developmental disorder in which a child’s head circumference is significantly smaller than expected for their age and gender. It is not a disease in itself, but a clinical sign that indicates impaired brain development. The team found that all six children had mutations in the same gene, TMEM167A. This suggested a single genetic cause for both the metabolic and neurological symptoms.

Understanding the Role of a Little-Known Gene

To better understand how this gene affects the body, Professor Miriam Cnop’s team at ULB used stem cells that were converted into beta cells in the pancreas, the cells responsible for insulin production. They also used gene editing techniques (CRISPR) to modify the TMEM167A gene. The experiments showed that when TMEM167A is damaged, the insulin-producing cells lose their normal functionality. When stress builds up in the cells, they activate internal stress responses that ultimately lead to cell death.

Dr. Elisa de Franco from the University of Exeter explained the significance of the results: “The discovery of the DNA changes that cause diabetes in babies offers us a unique opportunity to find the genes that play a key role in insulin production and secretion. In this joint study, the discovery of specific DNA changes that cause this rare form of diabetes in six children led us to elucidate the function of a little-known gene, TMEM167A, and show how it plays a key role in insulin secretion.”

Professor Cnop emphasized the far-reaching significance of the research, explaining: “The ability to generate insulin-producing cells from stem cells has enabled us to investigate the functional abnormalities in the beta cells of patients with rare forms and other types of diabetes. This is an exceptional model for researching disease mechanisms and testing treatment methods.”

Why can TMEM167A Cause Diabetes?

TMEM167A is crucial for the function of the Golgi apparatus, i.e., for the correct processing, packaging, and transport of proteins within the cell. This is particularly important for:

• Pancreatic beta cells that produce insulin
• Neurons, which have a very high protein turnover

Pathogenic TMEM167A mutations lead to:

• disrupted Golgi organization
• defective vesicular transport
• inadequate processing and release of insulin

Insulin cannot be produced properly or released correctly, even though some beta cells are present.

Why this Discovery is Significant Beyond Rare Diseases

The results show that the TMEM167A gene is crucial not only for insulin-producing beta cells, but also for neurons. At the same time, the gene appears to be less important for many other cell types. This finding helps to clarify the biological steps involved in insulin production and cell survival. The researchers say the work could also be important for studies of more common forms of diabetes, a disease that currently affects nearly 589 million people worldwide. The findings open up new perspectives for therapeutic approaches that target not only blood sugar regulation, but also the protection of the cellular transport and secretion systems of beta cells.

In the long term, such findings could help develop strategies that maintain the functionality of insulin-producing cells for longer, thereby slowing or preventing the progression of diabetes. In summary, research on TMEM167A shows that the vulnerability of beta cells and neurons is due to deeply rooted cell biological mechanisms. It makes it clear that diabetes—even in its common forms—is not only a metabolic disease, but also a disease of cellular organization and resilience, the understanding of which can open up new avenues for prevention and therapy.