🧬 Gene Summary: GLUD1
(Causing Hyperinsulinism/Hyperammonemia syndrome – HI/HA)
What does the GLUD1 gene do?
The GLUD1 gene provides instructions to make an enzyme called glutamate dehydrogenase (GDH). This enzyme helps cells in the pancreas sense nutrients—especially amino acids—and plays a role in deciding when insulin should be released.
How can changes in the GLUD1 gene cause hyperinsulinism?
Some changes in the GLUD1 gene make the GDH enzyme overactive. When this happens, the pancreas may release too much insulin, even when blood sugar is low or after eating protein-rich foods.
This leads to:
-
Low blood sugar (hypoglycaemia)
-
Higher-than-normal ammonia levels in the blood (hyperammonaemia)
This combination is known as Hyperinsulinism/Hyperammonemia (HI/HA) syndrome.
How common are changes in the GLUD1 gene in hyperinsulinism?
Variants in the GLUD1 gene are a well-known and relatively common cause of congenital hyperinsulinism, though they are less common than variants in the ABCC8 and KCNJ11 changes.
How are changes in the GLUD1 gene inherited?
GLUD1-related hyperinsulinism is usually inherited in a dominant pattern:
-
Dominant inheritance
-
One non-working copy of the gene can cause the condition
-
A parent may have mild symptoms or may not realize they are affected
-
-
New (de novo) changes
-
In some children, the gene change occurs for the first time and is not inherited from either parent
-
đź’ˇ A genetic counsellor can help explain what this means for your family and future children. See also our section on Inheritance.
What does a GLUD1 change mean for my child?
Children with GLUD1-related hyperinsulinism may:
-
Have low blood sugar beginning in infancy or early childhood
-
Be especially sensitive to protein-rich foods
-
Have mildly elevated ammonia levels (often without symptoms)
-
Experience symptoms ranging from mild to severe hypoglycaemia
Many children do very well with treatment, and learning triggers (such as protein sensitivity) can help families manage blood sugars.
How does this affect treatment?
Knowing a child has a GLUD1 gene change helps doctors:
-
Choose the right medication (most children respond well to diazoxide)
-
Avoid unnecessary pancreatic surgery (surgery is not typically helpful)
-
Give dietary guidance, including managing protein intake if needed
-
Monitor blood sugars and ammonia levels appropriately
This genetic diagnosis often leads to a clear and effective treatment plan.
Where can I learn more or get support?
-
Talk with your child’s hyperinsulinism care team
-
Meet with a genetic counsellor
-
Connect with hyperinsulinism family support organizations