Neonatal diabetes mellitus (NDM) is a disease that affects an infant and their bodys ability to produce or use insulin. NDM is a monogenic (controlled by a single gene) form of diabetes that occurs in the first 6 months of life. Infants do not produce enough insulin, leading to an increase in  glucose accumulation. It is a rare disease, occurring in only one in 100,000 to 500,000  live births. NDM can be mistaken for the much more common type 1 diabetes, but type 1 diabetes usually occurs later than the first 6 months of life. There are two types of NDM:  permanent neonatal diabetes mellitus (PNDM) is a lifelong condition. Transient neonatal diabetes mellitus (TNDM) is diabetes that disappears during the infant stage but may reappear later in life.Specific genes that can cause NDM have been identified. The onset of NDM can be caused by abnormal pancreatic development, beta cell dysfunction or accelerated beta cell dysfunction. Individuals with monogenic diabetes can pass it on to their children or future generations. Each gene associated with NDM has a different inheritance pattern. Symptoms and signs
The first sign of neonatal diabetes is often slowed fetal growth, followed by unusually low birthweight. At some point within the first six months of life, infants with neonatal diabetes tend to experience the classic symptoms of type 1 diabetes: thirst, frequent urination, and signs of dehydration. The timing of symptom onset varies with the type of neonatal diabetes.
Disease-associated variants of either subunit of KATP, KCNJ11 and ABCC8, can result in a channel that is "stuck open", rendering the β cell unable to secrete insulin in response to high blood glucose. Children born with disease-associated KATP variants often have intrauterine growth restriction and resulting low birthweight. Similarly, the second most common cause of permanent neonatal diabetes is alterations to the gene that encodes insulin. Mutations associated with neonatal diabetes tend to cause misfolding of the insulin protein; misfolded insulin accumulates in the endoplasmic reticulum (ER), leading to ER stress and β-cell death.Most transient neonatal diabetes is caused by the over-expression of a cluster of genes on chromosome 6, a region called 6q24. Over-expression of 6q24 is often caused by anomylous epigenetic regulation of the locus. The copy of 6q24 inherited from ones father normally has much higher gene expression than the copy inherited from ones mother. Therefore, inheriting two copies of the gene region from ones father (either through uniparental disomy, or receiving two copies from ones father in addition to the copy from ones mother) commonly results in over-expression of the locus. Alternatively, inheriting a maternal copy of 6q24 with defective DNA methylation can result in similar over-expression of the locus.Variants in several other genes can cause neonatal diabetes, though these cases are much rarer. Genetic changes that disable the transcription factors CNOT1, GATA4, GATA6, PDX1, PTF1A, or RFX6 – all involved in the development of the pancreas – result in a shrunken or missing pancreas.