About Congenital Hyperinsulinism
Congenital hyperinsulinism (HI) is the most frequent cause of severe, persistent hypoglycemia in newborn babies and children. In most countries, it occurs in approximately 1/28,000 births. About 60% of babies with HI develop hypoglycemia during the first month of life. An additional 30% will be diagnosed later in the first year and the remainder after that. With early treatment and aggressive prevention of hypoglycemia, brain damage can be prevented. However, brain damage can occur in children with HI if their condition is not recognized or if treatment is ineffective in the prevention of hypoglycemia. The material below explains the different forms of HI, the mechanisms of each type of HI, the genetic defects responsible for HI and their mode of inheritance. There is also information on treatment options and recent advances in diagnosis.
Mechanisms of Disease
Insulin is the most important hormone for controlling the concentration of glucose in the blood. As food is eaten, blood glucose rises and the pancreas secretes insulin to keep the blood glucose in the normal range. Insulin acts by driving glucose into the cells of the body. This action of insulin has two effects 1) maintaining blood glucose levels and 2) storing glucose particularly as glycogen in the liver. Once feeding is completed and the glucose levels fall, insulin secretion is turned off, allowing the stores of glucose in glycogen to be released into the bloodstream to keep blood glucose normal. In addition, with the switching off of insulin secretion, protein and fat stores become accessible and can be used instead of glucose as sources of fuel. In this manner, whether one eats or is fasting blood glucose levels remain in the normal range and the body has access to energy at all times.
With HI, however, this close regulation of blood glucose and insulin secretion is lost. The pancreas, which is responsible for insulin secretion, is blind to the blood glucose level and makes insulin regardless of the blood glucose concentration. As a result, the baby or child with HI can develop hypoglycemia at any time but particularly when fasting. In the most severe form of HI this glucose blindness causes frequent, random episodes of hypoglycemia.
HI causes a particularly damaging form of hypoglycemia because it denies the brain of all the fuels on which it is critically dependent. These fuels are glucose, ketones, and lactate. The usual protective measures against hypoglycemia, such as conversion of protein to glucose (called gluconeogenesis) and conversion of fat into ketones (called fatty acid oxidation and ketogenesis) are prevented by insulin. Once the brain cells are deprived of these important fuels, they cannot make the energy they need to work and so they stop working. The lack of appropriate fuel to the brain may result in seizures and coma and if prolonged may result in death of the cells. It is this cell damage which can manifest as a permanent seizure disorder, learning disabilities, cerebral palsy, blindness or even death.
Causes of Hyperinsulinism
A number of causes exist. Some forms will resolve and are considered transient. Others arise from genetic defects and persist for life. These genetic forms of HI do not go away, but in some cases, may become easier to treat as the child gets much older.
To learn more about the condition visit: https://congenitalhi.org/congenital-hyperinsulinism/
or https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/hyperinsulinism/