UCP-2 Hyperinsulinism

What is UCP-2 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).

Ordinarily, beta cells secrete just enough insulin to keep the blood sugar in the normal range. In children with HI, the secretion of insulin is not properly regulated, causing excess insulin secretion and low blood sugar.

UCP-2 hyperinsulinism is rare form of congenital HI that seems to be transient, meaning it is not a permanent condition, and eventually resolves over time.

Causes

UCP-2 hyperinsulinism is caused by a mutation in UCP-2 (uncoupling protein 2). Inheritance of the genetic defect is dominant, meaning only one parent must have a mutation of the gene to cause disease in the child.

Symptoms

Congenital hyperinsulinism causes 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.

Diagnosis

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.

History

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.

Treatment

UCP-2 hyperinsulinism is usually well-managed with a medicine called diazoxide (Proglycem). Reported cases of this rare form of HI resolve by 7 months to 6 years of age.

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.

charlotte

Stay in Touch

Subscribe to HI Hope, our e-newsletter for families.

mother holding son

Your Child's HI Appointment

Your first visit will be either an outpatient or inpatient visit, depending on your child’s needs.