Congenital Hyperinsulinism Center

What is Congenital HI?

Congenital hyperinsulinism (HI) is a disorder in which the insulin cells of the pancreas (beta cells) secrete too much insulin and at the wrong time. Excess insulin causes low blood sugar. Ordinarily, beta cells secrete just enough insulin to keep the blood sugar normal. With HI, the secretion of insulin is not properly regulated, causing excess insulin secretion and low blood sugar.

Normal blood sugar is 70 - 100 mg/dL. Anything less than 60 mg/dL is low, although severe symptoms due to hypoglycemia are not likely unless the blood sugar is below 50 mg/dL. Prolonged or severe low blood sugar can cause seizures or permanent brain damage.

Types of Hyperinsulinism

Researchers have uncovered several different types of HI. To date, genetic defects in four common genes have been identified: SUR1, KIR6.2, GK and GDH HI.

The four most common types of Congenital HI are:

KATP HI

This type of HI is caused by a defective SUR1 or KIR6.2 gene (SUR = Sulfonylurea Receptor; KIR6.2 = Potassium Channel).

The SUR1 and KIR6.2 genes are components of the KATP channel. The KATP channels (ATP-dependent potassium channels), which help to regulate insulin secretion in the beta cells, do not work properly in KATP HI.

Diffuse KATP HI

In this form of HI, all beta cells in the pancreas are affected. Infants with Diffuse KATP HI usually have extremely large birth weight and begin to have severe low blood sugar in the first days of life.

Diffuse KATP HI usually cannot be controlled with diazoxide medication. The treatment often includes octreotide, continuous dextrose, and/or surgery to remove 95% of the pancreas. The genetic defects in this type of Congenital HI are inherited in a recessive manner.

Focal KATP HI

In this form of HI, only a small, focal area of the pancreas is affected. The remainder of the beta cells in the pancreas are normal.

This type of HI is caused by a defective SUR1 or KIR6.2 gene in focal cells of the pancreas only. Potassium channels, which regulate insulin secretion in the beta cells, do not work properly in the focal beta cells.

The signs and symptoms are the same as Diffuse KATP HI in that this type often causes severe low blood sugar in the first days of life and large birth weight.

Focal KATP HI usually cannot be controlled with diazoxide medication. The treatment of focal KATP HI usually includes octreotide, continuous dextrose, and/or pancreatectomy. Focal KATP HI may potentially be cured if the focal area is surgically removed, because the remainder of the pancreas is normal.

The genetic defect in this type of HI is caused by a sporadic Loss of Heterozygosity (LOH).

Dominant KATP HI

This is a type of diffuse HI that is also caused by a defective SUR1 or KIR6.2 gene. However, these gene defects act in a dominant fashion and are usually responsive to medical treatment with diazoxide. This form of HI typically does not require surgery.

GDH HI

This type is caused by a defective GDH gene (GDH = Glutamate Dehydrogenase). GDH-HI is also known as hyperinsulinism/hyperammonemia syndrome (HI/HA).

With this type, the beta cells in the pancreas make too much insulin. This primarily occurs when the child fasts for too long or eats a meal of protein. Low blood sugar is triggered either by fasting or eating a protein meal.

The onset of hypoglycemia is often not in the newborn period. GDH-HI is also characterized by high ammonia levels in the blood. These high ammonia levels are not believed to be harmful.

GDH-HI is typically well controlled with diazoxide.

The genetic defect in GDH-HI is inherited in a dominant or sporadic manner.

GK HI

GK HI is a rare type of HI caused by a defective glucokinase (GK) gene. With GK HI, there is a disturbance in the ability of the pancreas to sense when blood sugar is too low. Secretion of insulin is, therefore, not turned off, and the blood sugar stays low. GK HI is less common than other types (only two families have been diagnosed). Some patients respond to diazoxide while others may require additional treatment.

The genetic defect in GK HI is inherited in a dominant or sporadic manner.

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Hyperinsulinism

Location of the pancreas in the human body. View more