Inheritance of focal forms of Hyperinsulinism.

The focal form of hyperinsulinism is inherited in a very complex manner. There are two events that take place. In the first instance the child inherits one abnormal gene from the father (who is the carrier). Secondly by an unknown mechanism some of the pancreatic-cells in the developing pancreas lose a tiny segment of chromosome 11. This segment that is lost contains very important genes which control the way cells divide. The loss of this segment causes these cells to divide more than the surrounding cells and cause the formation of a tiny focal lesion which causes too much insulin secretion. The risk of inheriting another child with focal disease is about 1%.

The most common cause of CHI is an abnormality in the proteins (called KATP channels) located in the pancreatic beta-cell. These channels normally control how much insulin is made in the beta-cell. Genetic abnormalities in these channels cause the beta-cell to make too much insulin. This is usually inherited in an autosomal recessive manner.

There also rare forms of CHI. These other forms include abnormalities in the enzymes Glucokinase (GK) and Glutamate Dehydrogenase (GDH). These enzymes increase the rate at which the pancreatic beta-cells work and hence make more insulin. In children with CHI, due to an abnormality in the enzyme GDH, the blood ammonia level is slightly raised. Abnormalities in these two enzymes are inherited in an autosomal dominant manner.

An even rarer form of CHI has been described where children have difficulty in breaking down fats to release energy. This is inherited in an autosomal recessive manner.