KATP Defect With Focal Congenital Hyperinsulinism

What is KATP defect with focal congenital hyperinsulinism?

Congenital hyperinsulinism (HI) is a genetic disorder in which the insulin cells of the pancreas, called beta cells, secrete too much insulin. Excess insulin causes low blood sugar (hypoglycemia).

In children with KATP defect with focal congenital hyperinsulinism, only an isolated, or focal, area of the pancreas is abnormal; the remainder of the pancreas is normal.


KATP defect with focal HI is caused by a defect in the SUR1 component of the KATP channel (SUR1= Sulfonylurea receptor; also known by its gene name, ABCC8).

The same type of disease can be caused by a defect in the other component of the potassium channel, Kir6.2 (Kir6.2= Potassium ion channel; also known by its gene name, KCNJ11).

This form of HI is the result of a “two-hit” genetic mechanism during early fetal life which created a loss of the KATP gene from the mother and a duplication of a mutation from the father. The genetic pattern is called “loss of heterozygosity” (LOH) and is different from recessive or dominant inheritance.


Children with KATP defect with focal HI may not be born with very large birth weight and profound hypoglycemia recognized in the first few days of life, so they may not be immediately recognized and may present later in the newborn period with seizures and low blood sugar (hypoglycemia).

The symptoms of hypoglycemia in infants are often difficult to identify, as they can be similar to normal infant activities.

Common symptoms of hypoglycemia include:

  • irritability
  • sleepiness
  • lethargy
  • excessive hunger
  • rapid heart rate

More severe symptoms, such as seizures and coma, can occur with a prolonged low blood sugar or an extremely low blood sugar. Common symptoms of hypoglycemia in older children include feelings of shakiness, weakness, tiredness, confusion, and rapid heart rate.

We consider a normal blood sugar to be >70 mg/dL. Anything less than 60 mg/dL is low, although severe symptoms due to hypoglycemia are not likely unless the blood sugar is less than 50 mg/dL. Prolonged or severe low blood sugar can cause seizures and permanent brain damage.


The diagnosis of congenital hyperinsulinism is based on history, laboratory findings, and genetic testing. Prompt diagnosis and establishment of effective treatment are essential to avoid neurologic damage. The diagnosis is made by evaluating the child's medical history, and the result of laboratory and genetic tests.


The history of the child is an important piece of the puzzle. This includes information such as when the low blood sugars started, the timing of the low blood sugars, whether the baby was born large for gestational age (LGA), any family history of low blood sugar or unexplained infant deaths.

Laboratory findings

Blood tests drawn when the blood sugar is less than 50 mg/dL are essential to the diagnosis of HI. In congenital HI, with a blood sugar <50, you will see suppressed ketones and free fatty acids, an elevated insulin level (although this may not always be captured), and a glycemic response to glucagon, with the blood sugar rising more than 30 mg/dL when glucagon is administered.

It is important that these samples at the time of a critically low blood sugar be obtained in an experienced, controlled environment, as we do not want a child to be kept with a critically low blood sugar longer than is absolutely necessary to make the diagnosis.

Genetic testing

The DNA from a blood sample from the child with congenital HI and each parent can be analyzed to screen for the mutations that cause the most common types of HI. This can be done at commercial laboratories and should be considered in any child suspected to have congenital HI. Contact us for more information on where to have this testing performed. 18F-DOPA PET scan can reveal an area of increased uptake, suggestive of a focal lesion, which provides crucial guidance to the surgeon who will be looking for the focal lesion


Treatment for children with KATP defect with focal HI typically involves partial pancreatectomy for removal of the focal lesion. There is a very high potential for a cure if the focal area is surgically removed. Our cure rate at CHOP over the past 10 years is 95 percent.

Children with this form of HI usually cannot be treated with diazoxide (Proglycem) medication.

Long-term outcomes

We are now tracking and compiling data on the long-term outlook for children with Congenital HI. We know that with rapid diagnosis and appropriate treatment, keeping blood sugars >70 mg/dL, it is less likely that children with congenital HI will have long-term effects of hypoglycemia. With focal hyperinsulinism, 94 percent of children are cured with surgery.


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