Doctors have found a new cause of diabetes in babies that appear in the first few months of life. An international team of scientists pinpointed changes in a gene called TMEM167A in six children from different families. These changes stop insulin-making cells in the pancreas from working right, leading to high blood sugar levels. The babies also face brain and nerve problems because the same gene plays a role there too. The work came from teams at the University of Exeter Medical School in England and Université Libre de Bruxelles in Belgium, using the latest DNA tools and lab-grown cells.
Background
Diabetes in newborns shows up before six months old and differs from the usual types seen in kids or adults. Most cases stem from gene problems passed from parents, not the body's immune system attacking cells like in type 1 diabetes. In about half of these baby cases, the high blood sugar goes away after some months, but it can come back later. Doctors call the passing kind transient neonatal diabetes. Finding the exact gene fault helps families get a clear answer and plan care.
For years, researchers knew of a few genes tied to this baby diabetes, but many cases stayed unexplained. This new find adds to the list after a long search. The six children all had the same TMEM167A changes, one from each parent, which is common in these rare genetic conditions. Before this, genes like IER3IP1 and YIPF5 linked to a group of symptoms including diabetes and brain issues, known as MEDS syndrome. Now TMEM167A joins as the third cause for that set of problems.
The study built on work over the past decade. Teams looked at DNA from babies with unexplained diabetes. They found this gene popping up in cases that puzzled doctors for years. Neonatal diabetes affects very few babies, making it hard to spot patterns. But each discovery like this one fills in gaps about how the body handles sugar from the start of life.
Key Details
The scientists sequenced DNA from the six babies and saw the TMEM167A mutations every time. To check what the gene does, they grew stem cells into pancreas beta cells, the ones that make insulin. They used CRISPR tools to swap in the faulty gene version from one baby. Those cells could not release insulin properly. They got stressed and died off, raising blood sugar.
How the Gene Affects Cells
Beta cells need TMEM167A to stay healthy and pump out insulin when sugar levels rise. Without it working right, the cells fail fast. The gene matters more in pancreas and brain cells than in others. That explains why these babies get diabetes plus nerve troubles like weak muscles or developmental delays. Lab tests on mouse and human cells showed the gene active in both places from birth through adulthood.
The team tested cells from the patients' own stem cells turned into beta cells. This let them watch the problem in action. Normal cells handled sugar spikes fine. Faulty ones could not keep up. Stress signals built up inside, killing the cells over time.
"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 from the University of Exeter. "In this collaborative study, the finding of specific DNA changes causing this rare type of diabetes in six children led us to clarifying the function of a little-known gene, TMEM167A, showing how it plays a key role in insulin secretion."
"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," said Professor Miriam Cnop from Université Libre de Bruxelles. "This is an extraordinary model for studying disease mechanisms and testing treatments."
Doctors already used the findings for two families. They gave genetic tests confirming the cause, helping with treatment plans and watching for diabetes return.
What This Means
This work points to steps in insulin making that can break down. TMEM167A helps beta cells survive and respond to sugar. Lessons from these rare baby cases apply to common diabetes too. Over 589 million adults live with diabetes today, mostly type 2 where beta cells wear out over time. Understanding this gene might lead to ways to protect those cells.
For brain health, the gene link suggests shared paths between sugar control and nerve function. Babies with this face developmental issues, so early checks matter. Genetic tests now include more genes like this one. Panels check over 30 genes for neonatal diabetes, plus others for related problems.
Families get real help from knowing the cause. Treatment often means insulin shots at first. For transient cases, it stops, but monitoring continues. This find speeds diagnosis for others with matching symptoms. Researchers plan more work on similar gene spots found in other families.
The discovery changes how doctors view baby diabetes. It shows one gene can hit both metabolism and brain at once. Stem cell models open doors to test drugs directly on patient cells. That could mean tailored care sooner. Broader diabetes studies gain from seeing beta cell failure up close. Efforts continue to map all causes, helping the tiniest patients and adults alike.
