Scientists uncover a hidden type of diabetes in newborns

Using cutting-edge 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 led by the University of Exeter Medical School in collaboration with Université Libre de Bruxelles (ULB) in Belgium, along with other international partners. Together, the team determined that mutations in a gene called TMEM167A are responsible for this rare type of neonatal diabetes.

Some infants develop diabetes within the first six months of life. In more than 85 percent of these cases, the condition is caused by inherited changes in DNA. In the new study, researchers examined six children who not only had diabetes but also showed neurological conditions such as epilepsy and microcephaly.

The team found that all six children shared mutations in the same gene, TMEM167A. This pointed to a single genetic cause behind both the metabolic and neurological symptoms.

To better understand how this gene affects the body, Professor Miriam Cnop's team at ULB used stem cells that were transformed into pancreatic beta cells, the cells responsible for making insulin. They also applied gene-editing techniques (CRISPR) to alter the TMEM167A gene.

The experiments showed that when TMEM167A is damaged, insulin-producing cells lose their ability to function normally. As stress builds inside the cells, they activate internal stress responses that ultimately lead to cell death.

Dr. Elisa de Franco, at the University of Exeter, explained the significance of the findings: "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. In this collaborative study, the finding of specific DNA changes causing this rare type of diabetes in 6 children, led us to clarifying the function of a little-known gene, TMEM167A, showing how it plays a key role in insulin secretion."

Professor Cnop emphasized the broader impact of the research, saying: "The ability to generate insulin-producing cells from stem cells has enabled us to study what is dysfunctional in the beta cells of patients with rare forms as well as other types of diabetes. This is an extraordinary model for studying disease mechanisms and testing treatments."

The findings reveal that the TMEM167A gene is critical 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 insight helps clarify the biological steps involved in insulin production and cell survival.

Researchers say the work could also inform studies of more common forms of diabetes, a condition that currently affects nearly 589 million people worldwide.

The study received support from Diabetes UK, the European Foundation for the Study of Diabetes and Novo Nordisk foundation, the ULB Foundation, the FNRS, the FRFS-WELBIO, the Research Foundation Flanders (FWO) and the Excellence of Science (EOS) program. Dr. De Franco is supported by the NIHR Exeter Biomedical Research Centre.

The research paper is titled 'Recessive TMEM167A variants cause neonatal diabetes, microcephaly and epilepsy syndrome', and it appears in The Journal of Clinical Investigation.