Why do some babies develop diabetes within months of birth: A newly identified gene reveals a hidden cause of neonatal disease

The first few months of life are a very important period in terms of human development, and at this point, many of the most severe diseases occurring in infancy are still poorly understood,” says Dr. Billag, a researcher in the field. Neonatal diabetes is one of the diseases affecting infants in the first six months of life. It is a rare condition and can be a severe source of distress to parents. Now, for the first time, a novel mechanism for the development of diabetes in neonates has been identified. Researchers at the University of Exeter Medical School have identified for the first time a novel gene underlying diabetes in neonates. They show changes in a so far poorly characterised gene affect the function of “insulin-producing cells in the first months of life, which contributes to diabetes in early life.”Neonatal diabetes is different from the well-known forms that occur in children and adults. It manifests during the first six months of an infant's life, and in most instances, rare genetic mutations are the primary cause rather than lifestyle factors and autoimmune responses. For this particular study, the researchers carefully selected six children from various regions who experienced diabetes as babies, along with additional neurological symptoms, including epilepsy and severe congenital microcephaly.Through DNA analysis, the team found that a genetic difference in the same gene, named TMEM167A, was present in all six children. But this gene had no previous connection to diabetes. The reappearance of this gene across random patients suggested a strong connection to diabetes, as it could contribute to insulin problems being developed within individuals. Insulin is produced by specialised cells called beta cells in the pancreas. Beta cells must fold, package, and secrete insulin in a way to maintain blood sugar levels within a certain range. Research has shown that the protein TMEM167A is particularly important in this regard. Beta cells have difficulty dealing with the cellular stress of insulin production when the gene is mutated.Instead of working properly, these cells trigger stress pathways and end up damaging and dying. As a result of having very few functional beta cells, insulin is no longer produced at a high enough level to ensure there is no diabetes at a tender age. To see how this affected beta cells, researchers from Université Libre de Bruxelles set out to work with stem cells in order to first differentiate these cells into insulin-secreting beta cells, then destroy the TMEM167A gene by working with the use of gene editing.With this method, scientists could see, in detail, where and why insulin secretion went awry when damage occurred to this gene. Since there was too much for these cells to handle, stress responses took over, and their capacity to survive disappeared altogether. Not only did this lab technique yield results that would reveal why beta-cell malfunction is associated with TMEM167A in a way that simply would not be possible in humans, but it also allowed scientists to observe both these cells and insulin secretion in ways that would not have been achievable in their lab or in nature in such detail.A crucial part of the discovery is that TMEM167A has a high level of necessity not only in beta cells but also in some neurons. This solves the puzzle of how the children were suffering from both diabetes and some form of neuropathy. The TMEM167A gene plays a crucial part in cells that demand a high level of protein synthesis and secretion, like insulin-secreting cells and neurons, while having a less crucial part in other cells. This dual-function presentation underlines how one genetic alteration may dually interfere with several biological systems within developing organisms and create complicated medical situations.