Carbamoyl phosphate synthetase I deficiency
Carbamoyl phosphate synthetase I deficiency is an inherited metabolic disorder that prevents the body from processing nitrogen, leading to the accumulation of toxic ammonia in the blood.
Overview
Carbamoyl phosphate synthetase I deficiency causes hyperammonemia, an accumulation of ammonia in the blood. Ammonia is a byproduct of protein breakdown and is toxic at high levels, particularly to the brain.
Symptoms
Infants typically show signs of hyperammonemia within the first few days of life. Symptoms include:
- Unusual sleepiness
- Poorly regulated breathing or body temperature
- Unwillingness to feed
- Vomiting after feeding
- Unusual body movements
- Seizures or coma
Survivors may experience recurring symptoms if diet is not managed or during periods of stress or infection. Long-term effects can include delayed development and intellectual disability. In some cases, symptoms may be less severe and appear later in life.
Causes
The condition is caused by mutations in the CPS1 gene, which provides instructions for making the enzyme carbamoyl phosphate synthetase I. This enzyme is critical for the urea cycle, a sequence of reactions that processes excess nitrogen from protein breakdown into urea for excretion by the kidneys.
When this enzyme is deficient or absent, the urea cycle cannot function, causing nitrogen to accumulate as toxic ammonia. This buildup is particularly damaging to the brain, resulting in the neurological symptoms associated with the disorder.
Inheritance
This condition is inherited in an autosomal recessive pattern. This means both copies of the gene in each cell must have mutations to cause the disorder. Parents of an affected individual each carry one copy of the mutated gene but typically do not exhibit symptoms.