Neonatal diabetes mellitus (NDM) is a disease that affects an infant and their body's ability to produce or use insulin. NDM is a kind of diabetes that, along with maturity onset diabetes of the young is monogenic (regulated by a single gene) and arises 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), a lifelong condition, and transient neonatal diabetes mellitus (TNDM), a form of 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.
Signs and symptoms 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. Those with transient neonatal diabetes tend to have symptoms in the first few days or weeks of life, with affected children showing weight loss and signs of dehydration, along with high levels of sugar in the blood and urine. Some children also have high levels of ketones in the blood and urine, or signs of metabolic acidosis. Permanent neonatal diabetes starts slightly later, typically around six weeks of age. Regardless of type, preterm infants tend to experience symptoms earlier, typically around one week of age. Neonatal diabetes is classified into three subtypes: permanent, transient, and syndromic; each with distinct genetic causes and symptoms. Syndromic neonatal diabetes is the term for diabetes as just one component of any of several complex syndromes that affect neonates, including IPEX syndrome, Wolcott-Rallison syndrome, and Wolfram syndrome. Symptoms vary widely based on the syndrome.
Complications People with KATP channel variations are at increased risk of developing attention deficit hyperactivity disorder, sleep disruptions, seizures, and experiencing developmental delay – all due to the presence of KATP channels in the brain. These can range from unnoticeably mild to severe, and can sometimes improve with sulfonylurea treatment. Those with 6q24 overexpression tend to have transient diabetes, with hyperglycemia tending to disappear within the first year of life. Despite the return of euglycemia, people with 6q24 overexpression are at high risk of developing diabetes later in life, as teenagers or adults. Many of the genetic variations that cause neonatal diabetes are inherited in an autosomal dominant manner, i.e. receiving a single copy of the disease-associated variant results in disease. This is the case for the KATP genes KCNJ11 and ABCC8, and paternally inherited 6q24 amplifications, any of which have a 50% chance of being transmitted to each offspring of an affected individual.
Cause Neonatal diabetes is a genetic disease, caused by genetic variations that were either spontaneously acquired or inherited from one's parents. At least 30 distinct genetic variants can result in neonatal diabetes. The development and treatment of neonatal diabetes will vary based on the particular genetic cause. Known genetic variants cause neonatal diabetes by five major mechanisms: Preventing the development of the pancreas or β cells, promoting β-cell death by autoimmunity or endoplasmic reticulum stress, preventing β cells from recognizing glucose or secreting insulin, or abnormal expression of the 6q24 region on chromosome 6.
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