Familial hyperinsulinism is a disorder characterized by disrupted insulin response, where the pancreas secretes insulin even without carbohydrate consumption.
This excess insulin can lead to dangerously low blood sugar levels (hypoglycemia). Infants with this condition often experience low blood sugar shortly after birth, leading to feeding difficulties, poor muscle tone, and breathing problems. Immediate glucose infusions are necessary to prevent seizures, and prolonged hypoglycemia can cause permanent brain damage. In some cases, symptoms of familial hyperinsulinism may appear later in childhood and vary in severity among individuals, even within the same family. The disorder is caused by mutations in the KCNJ11 gene. Rarely, specific mutations in this gene can also lead to neonatal diabetes, where insufficient insulin secretion results in dangerously high blood sugar levels (hyperglycemia). Infants with neonatal diabetes may be smaller at birth, experience feeding difficulties, dehydration, glucose in the urine, and excessive urination. Treatment may be lifelong for some, while others may have symptoms resolve after a few weeks or months. Rare neurological symptoms, such as developmental delay and seizures, can occur.
As noted above, this group of conditions is caused by pathogenic (disease-causing) variants in the KCNJ11 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
In very rare cases, a single mutation in KCNJ11 can cause dominant neonatal diabetes, putting carriers at risk for diabetes.