Congenital hyperinsulinism
Congenital hyperinsulinism is a condition characterized by the over-secretion of insulin, leading to frequent and dangerous episodes of low blood sugar.
Overview
Congenital hyperinsulinism causes the body to produce abnormally high levels of insulin, a hormone that regulates blood glucose. Because insulin is secreted regardless of blood glucose levels, individuals experience frequent hypoglycemia (low blood sugar), which can lead to severe neurological and physical complications if left untreated.
Symptoms
Symptoms often appear in infancy or early childhood and include:
- Lethargy or lack of energy
- Irritability
- Difficulty feeding
- Seizures
- Breathing difficulties
- Coma (in severe cases)
Repeated episodes of hypoglycemia increase the risk of long-term complications such as intellectual disability, vision loss, and brain damage.
Causes
The condition is caused by mutations in genes that regulate insulin secretion from beta cells in the pancreas. In healthy individuals, insulin secretion is tightly controlled by glucose levels. In those with congenital hyperinsulinism, beta cells release insulin even when blood glucose is low, causing glucose to be rapidly removed from the bloodstream and depriving the brain of its primary fuel source.
Mutations in the ABCC8 and KCNJ11 genes are the most common causes. Other associated genes include GCK, HADH, HNF1A, and HNF4A.
Types and Inheritance
There are two primary forms of the condition:
- Diffuse Form: All beta cells in the pancreas secrete too much insulin. This is most often inherited in an autosomal recessive pattern, though it can occasionally be autosomal dominant.
- Focal Form: Only a subset of beta cells over-secrete insulin. This form has a more complex inheritance pattern, often involving an inherited inactive gene from the father combined with a new (de novo) mutation that occurs during embryonic development.