KCNJ11-related familial hyperinsulinism

What Is KCNJ11-Related Familial Hyperinsulinism?

Familial hyperinsulinism is an inherited condition of disrupted insulin response. In a healthy individual, the pancreas normally secretes a hormone called insulin in response to rising blood sugar after eating carbohydrates. In familial hyperinsulinism, insulin is secreted even without carbohydrate consumption. An excess of insulin released into the blood can cause blood sugars to drop to dangerously low levels (hypoglycemia). One cause of familial hyperinsulinism is due to mutations in the KCNJ11 gene.

Infants with familial hyperinsulinism tend to have significantly low blood sugar within the first few days of life. These newborns are typically larger at birth and may have difficulty feeding, poor muscle tone, and breathing problems. These infants often require immediate infusions of glucose to help raise blood sugar levels and prevent seizures. Prolonged hypoglycemia can also lead to permanent brain damage.

In some individuals with familial hyperinsulinism, symptoms do not appear until later in childhood. The low blood sugar associated with the condition can also range from mild to severe depending on the individual, and it can vary even among members of the same family.

Additional Findings

Rarely, specific mutations in the KCNJ11 gene cause neonatal diabetes. In neonatal diabetes, not enough insulin is secreted, and blood sugar increases to dangerously high levels (hyperglycemia). Infants with neonatal diabetes tend to have high blood sugar levels between birth and six months of age. These newborns are typically smaller at birth than normal and may have difficulty feeding, severe dehydration, glucose in the urine, and excessive urination. While some with neonatal diabetes need lifelong treatment to prevent high blood sugar, others may not experience symptoms after a few weeks or months. Although rare, some infants may also have neurological symptoms, which can include developmental delay, muscle weakness, and seizures. Similar to familial hyperinsulinism, symptoms of neonatal diabetes can range from mild to severe, and severity can vary among family members. In rare cases, a single mutation in KCNJ11 causes dominant neonatal diabetes. A dominant condition is one where only one mutation is sufficient to cause the condition. In these cases, carriers may be at risk for diabetes.

How Common Is KCNJ11-Related Familial Hyperinsulinism?

Several genes are known to cause familial hyperinsulinism with KCNJ11 mutations accounting for up to 5% of all familial hyperinsulinism. The overall incidence of hyperinsulinism is approximately 1 in 50,000 people. It is more common among individuals of Finnish and Saudi Arabian descent, where the disease may affect as many as 1 in 2,675 individuals.

How Is KCNJ11-Related Familial Hyperinsulinism Treated?

Treatment for familial hyperinsulinism includes dietary modification, medications, and surgical intervention. If an infant shows symptoms of familial hyperinsulinism at birth, intravenous glucose is often given to raise and stabilize the blood sugar level. Infants may also need frequent feedings with large amounts of carbohydrates, even overnight. A feeding tube may be helpful to ensure that an infant receives sufficient quantities of carbohydrates, and can help facilitate automatic feedings overnight.

There are also several types of medications to manage familial hyperinsulinism. Most of these medications focus on reducing the amount of insulin that is released into the body. Surgery may be needed to remove part of the pancreas if diet and medication cannot sufficiently manage a patient's blood sugar levels.

After an extended period of successful treatment, many with familial hyperinsulinism find that their symptoms lessen in severity or even go into remission. However, individuals with familial hyperinsulinism may find their symptoms aggravated by viral infections and should take particular precautions when they become ill, even if their symptoms have gone into remission. They should also avoid long periods of time without eating.

What is the Prognosis for an Individual with KCNJ11-Related Familial Hyperinsulinism?

The long-term outlook for an individual with familial hyperinsulinism depends upon the severity of the symptoms and the vigilance of the efforts to treat it. Permanent brain damage can occur from episodes of low blood sugar. Even with treatment, those with the disease can develop some degree of brain damage or have learning difficulties. They also may be at an elevated risk of diabetes. In the most serious cases, when the disease is not recognized and properly treated, it can be fatal. With early diagnosis and careful treatment, individuals with familial hyperinsulinism can have normal lifespans.