N-acetylglutamate synthase deficiency
N-acetylglutamate synthase deficiency is a rare urea cycle disorder that leads to the toxic accumulation of ammonia in the blood, which can cause severe neurological damage.
Description
N-acetylglutamate synthase deficiency is a disorder that causes abnormally high levels of ammonia to accumulate in the blood. Ammonia is a byproduct of protein breakdown and is toxic at high levels, particularly to the brain.
In infants, symptoms often appear in the first few days of life, including:
- Lack of energy (lethargy)
- Unwillingness to eat
- Difficulty controlling breathing rate or body temperature
- Seizures
- Unusual body movements
- Coma
Complications can include developmental delay and intellectual disability. In later-onset cases, symptoms such as vomiting, lack of coordination, headaches, confusion, and behavioral changes may be triggered by high-protein intake, illness, or stress.
Frequency
This is a very rare disorder, estimated to affect fewer than 1 in 2 million people worldwide.
Causes
Mutations in the NAGS gene cause this condition. It is a urea cycle disorder, meaning it disrupts the process that breaks down excess nitrogen from protein metabolism into urea for removal from the body. The NAGS gene provides instructions for the enzyme N-acetylglutamate synthase, which is essential for the first step of the urea cycle. A deficiency of this enzyme impairs the cycle, leading to a buildup of ammonia that damages brain tissue.
Gene Associated with N-acetylglutamate synthase deficiency
- NAGS
Inheritance
This condition is inherited in an autosomal recessive pattern. Both copies of the gene in each cell must have mutations for the disorder to occur. Parents of an affected individual each carry one copy of the mutated gene but typically remain asymptomatic.
Other Names
- Hyperammonemia, type III
- N-acetylglutamate synthetase deficiency
- NAGS deficiency