What is Congenital Hyperinsulinism?

Congenital Hyperinsulinism (CHI) is a rare genetic disorder where the pancreas produces excessive insulin. This causes low blood sugar (hypoglycemia), which can lead to a variety of symptoms and, if not treated, may cause serious health complications, including brain damage or even seizures. The condition typically presents in infancy or early childhood, though it can also be diagnosed later in life.

The pancreas normally releases insulin to regulate the body’s blood sugar levels, but in individuals with CHI, the pancreas releases too much insulin, leading to dangerously low blood sugar levels. Insulin is essential for the body to convert glucose into energy, but excessive amounts can cause glucose levels to drop to abnormally low levels, affecting the brain and other vital organs.

What Causes Congenital Hyperinsulinism?

Congenital Hyperinsulinism is caused by genetic mutations that affect the regulation of insulin release from the pancreas. These mutations affect the cells in the pancreas that are responsible for insulin production. As a result, the cells release more insulin than the body needs, causing low blood sugar levels.

CHI can be inherited in an autosomal recessive or autosomal dominant pattern, depending on the specific genetic mutation. In autosomal recessive inheritance, both parents must carry the defective gene, whereas in autosomal dominant inheritance, only one parent needs to carry the defective gene for the condition to be passed on to the child.

The two main forms of CHI are:

• Diffuse CHI: The condition affects the entire pancreas, leading to widespread overproduction of insulin.
• Focal CHI: The condition is confined to one part of the pancreas, and often, surgery can be performed to remove the affected tissue.

What Are the Symptoms of Congenital Hyperinsulinism?

The symptoms of Congenital Hyperinsulinism are primarily related to low blood sugar (hypoglycemia), and can range from mild to severe. Some common symptoms include:

• Severe hypoglycemia: Low blood sugar levels can cause symptoms such as dizziness, confusion, irritability, weakness, and fatigue.
• Seizures: If blood sugar drops too low, it can cause seizures due to insufficient glucose for brain function.
• Poor feeding and lethargy: Infants may show poor feeding habits and appear unusually tired or inactive.
• Tremors or shaking: Low blood sugar levels can cause shaking or tremors, particularly in infants.
• Rapid heart rate: The heart may beat faster than normal in response to low glucose levels.
• Sweating: Excessive sweating can occur as the body attempts to counteract low blood sugar levels.
• Pale skin: Infants with hypoglycemia may appear pale due to low glucose levels in the bloodstream.

In severe cases, untreated hypoglycemia can lead to brain damage, developmental delays, and intellectual disabilities.

How is Congenital Hyperinsulinism Diagnosed?

Diagnosing Congenital Hyperinsulinism involves a combination of medical history, physical examination, and specialized tests. Some of the diagnostic methods include:

• Blood tests: These tests measure glucose and insulin levels in the blood. In CHI, blood sugar levels are low, while insulin levels are abnormally high.
• Genetic testing: Genetic testing is used to identify mutations in the genes responsible for CHI. This can help confirm the diagnosis and determine the type of CHI.
• Imaging tests: Imaging such as ultrasound or CT scans may be used to locate areas of the pancreas that are overproducing insulin (particularly in focal CHI).
• Intravenous glucose test: A test where glucose is administered intravenously while monitoring blood sugar and insulin levels can help confirm the diagnosis.

In some cases, continuous glucose monitoring may be used to observe fluctuations in blood sugar levels over time.

How is Congenital Hyperinsulinism Treated?

The treatment of Congenital Hyperinsulinism focuses on maintaining normal blood sugar levels and preventing severe hypoglycemia. The approach to treatment depends on the severity of the condition and whether it is diffuse or focal. Treatment options include:

1. Medications:
   • Diazoxide: A medication that helps to inhibit insulin release from the pancreas and raise blood sugar levels.
   • Octreotide: A drug that can help control insulin secretion.
   • Glucagon: This hormone can be used to increase blood sugar levels in emergency situations, such as during a hypoglycemic episode.
2. Dietary management:
   • Frequent feedings with high-sugar content are essential to prevent hypoglycemia in infants.
   • For older children and adults, a high-protein and complex carbohydrate diet may help maintain more stable blood sugar levels.
3. Surgical treatment:
   • In cases of focal CHI, surgery may be necessary to remove the part of the pancreas that is overproducing insulin. This surgery is often successful in resolving the hypoglycemia.
   • Pancreatectomy: In severe cases of diffuse CHI, part of the pancreas may need to be removed to control insulin production.
   • Islet cell transplantation: In some cases, where surgery is not successful, islet cell transplantation may be considered to restore normal insulin function.
4. Emergency care:
   • For infants and children experiencing severe hypoglycemia, glucose may be administered intravenously, and emergency interventions may be required.
5. Ongoing monitoring: Long-term management may include regular blood sugar monitoring and continuous assessment by a medical team to ensure proper insulin regulation and overall health.

What is the Outlook for People with Congenital Hyperinsulinism?

The outlook for individuals with Congenital Hyperinsulinism varies depending on the severity of the condition and how well it is managed. With early diagnosis and appropriate treatment, most children with CHI can lead a normal life, but some may experience long-term challenges, including:

• Intellectual and developmental delays: In cases where hypoglycemia is not well controlled, brain damage can occur, potentially leading to intellectual or developmental delays.
• Growth issues: Some children may have growth problems, especially if the condition has been poorly managed in infancy.
• Lifelong management: Many individuals with CHI will require ongoing medical supervision, including blood sugar monitoring, and may need medications to help manage insulin production.

With early intervention and proper treatment, however, many individuals with congenital hyperinsulinism go on to live healthy, active lives.

Can Congenital Hyperinsulinism Be Prevented?

Since Congenital Hyperinsulinism is a genetic condition, it is not preventable. However, early genetic counseling can help families understand their risk if they have a history of CHI. Prenatal genetic testing may be recommended for families with a known history of the condition to assess the risk of CHI in a future pregnancy.

Who is at Risk for Congenital Hyperinsulinism?

Congenital Hyperinsulinism is inherited and typically runs in families. The primary risk factors include:

• Family history: Children with parents who carry genetic mutations associated with CHI are at higher risk.
• Genetic mutations: Specific mutations in genes such as ABCC8, KCNJ11, and others are associated with CHI.