For a small group of newborns, symptoms that arise in the early days of life suggest a deeper issue: a rare form of diabetes that impacts both the brain and the pancreas right from birth.
When Diabetes Appears in Infancy
While most people associate diabetes with childhood, adolescence, or adulthood, neonatal diabetes breaks that norm. It manifests within the first six months of life, sometimes as early as the first few days. These infants struggle to regulate blood sugar levels almost immediately upon birth.
Genetics play a significant role in neonatal diabetes. In over 80% of affected babies, a mutation in a single gene disrupts insulin production, preventing the pancreas from releasing enough of this vital hormone that controls blood sugar.
However, diabetes is not always the only symptom. Some infants experience seizures, abnormal muscle tone, or microcephaly (a smaller-than-average head size). These symptoms point to significant brain involvement. As a result, affected babies may later face developmental delays, learning difficulties, or severe epilepsy.
For a small subset of newborns, diabetes serves as the first visible sign of a more complex disorder involving both the brain and pancreas.
MEDS Syndrome: A Rare Genetic Condition
When neonatal diabetes, epilepsy, and brain abnormalities appear together, clinicians identify a rare condition known as MEDS syndrome. For many years, only two genes were recognized as being linked to this condition. However, recent developments have changed this understanding.
The Discovery of TMEM167A
In 2025, a European research team studying six children with neonatal diabetes, microcephaly, and frequent epilepsy made a groundbreaking discovery. All six children carried damaging variants of the same gene: TMEM167A. This gene had previously been overlooked in genetic databases, with little known about its role.
The mutations were recessive, meaning each child inherited one faulty copy from each parent. Interestingly, the parents, who carried only one mutated copy, were healthy, supporting the theory that TMEM167A played a key role in the disease.
The Role of TMEM167A in Early Development
Further research revealed that TMEM167A is highly active in two organs during early human development: the brain and pancreas.
In early brain development, TMEM167A is particularly active in “neurogenic zones,” areas where new neurons are formed. These include the pallium (which gives rise to the cerebral cortex) and the basal ganglia, which are involved in movement and cognition.
Studies using brain organoids—miniature, lab-grown brain structures—showed that TMEM167A is crucial for the proper functioning of neural stem cells. When this gene is faulty in these stem cells, the brain may be smaller and less structured, increasing the risk of seizures and other neurological issues.
Impact on the Pancreas
TMEM167A’s role in the pancreas mirrors its function in the brain. During early gestation, the gene is active throughout pancreatic tissue, including in progenitor cells and the endocrine cells that eventually develop into insulin-producing beta cells.
When researchers studied human pancreatic samples, they found that TMEM167A’s activity coincided with insulin production, suggesting its role in hormone production.
In laboratory experiments, human stem cells with a TMEM167A mutation were engineered to become beta-like pancreatic cells. These mutated cells showed a breakdown in the internal “shipping system” that transports proteins, including proinsulin, to where they are processed into functional insulin.
Without this system working properly, proinsulin accumulates, and the cells struggle to produce insulin. This results in reduced insulin production and increased cellular stress, leading to premature cell death.
From Lab to Animal Models: Testing the Mutation
Researchers then transplanted these defective beta-like cells into mice. In theory, these grafts should restore insulin secretion, but the cells barely released any insulin at all, confirming that TMEM167A is essential for proper insulin function.
While this discovery is concerning, it also offers a glimmer of hope. When the cells were treated with certain compounds, including exendin-4 (a GLP-1 analog used in type 2 diabetes) and imeglimin (an experimental metabolic agent), cellular stress decreased, and cell survival improved, despite the genetic defect.
Why TMEM167A Matters for Families and Clinicians
For parents facing neonatal diabetes in an intensive care setting, the discovery of TMEM167A provides important insights. Identifying this gene allows for a more precise diagnosis and helps predict recurrence risk, as the mutation is recessive. If both parents carry the mutation, there is a 25% chance their future children may also be affected.
With a confirmed diagnosis, doctors can closely monitor neurological issues and plan early interventions such as physiotherapy, speech therapy, and epilepsy management. Instead of focusing solely on blood sugar levels, clinicians can prepare for a comprehensive brain-pancreas syndrome that starts in the womb.
Broadening Our Understanding of Disease
TMEM167A now joins a growing list of genes that connect endocrine diseases with neurodevelopmental disorders. This shift encourages researchers to consider how shared molecular pathways affect multiple systems during development.
Key Concepts in the Research
- Neonatal diabetes: A form of diabetes diagnosed in the first six months of life, typically caused by a single genetic mutation.
- Microcephaly: A condition characterized by a significantly smaller-than-average head, often indicating limited brain growth.
- Recessive mutation: A genetic change that leads to disease only when both copies of the gene are affected.
- Endoplasmic reticulum–Golgi transport: The internal process by which newly created proteins are processed and transported within cells.
- Organoid: A lab-grown, three-dimensional model of an organ used for research.
Looking Ahead: Implications for Future Care
Although targeted therapies for TMEM167A-related diseases are still a long way off, the research holds promise. The condition is extremely rare, and any potential treatments would need to reach both the brain and pancreas early in development. Challenges like timing, safety, and delivery of therapy to a developing fetus or newborn add to the complexity.
In the meantime, the research offers a pathway for clinicians. Rapid genetic testing for neonatal diabetes combined with neurological symptoms could help identify TMEM167A mutations early, sparing families from a prolonged diagnostic journey.
On a broader scale, this discovery challenges the way childhood diseases are classified. A single gene mutation like TMEM167A cannot be neatly categorized as purely neurological or endocrine. It highlights the interconnected nature of development, where genetic mutations can affect multiple organ systems.
For families, understanding this genetic connection can help visualize the problem as an issue with the cell’s internal “logistics.” When proteins such as proinsulin cannot be properly transported within cells, the entire organ suffers. In the brain, fewer neurons form; in the pancreas, beta cells malfunction. While the symptoms differ, the underlying cause is the same.
