From the FDA Drug Label
Urea cycle disorders can result from decreased activity of any of the following enzymes: N-acetylglutamate synthetase (NAGS), carbamyl phosphate synthetase (CPS), argininosuccinate synthetase (ASS), ornithine transcarbamylase (OTC), argininosuccinate lyase (ASL), or arginase (ARG) These disorders vary in severity and may be first detected at various ages, from newborn infants to adults. They lead to increased amounts of ammonia in the blood, which may cause disturbed brain function and severe brain damage.
The causes of hyperammonemia include:
- Urea cycle disorders due to decreased activity of enzymes such as:
- N-acetylglutamate synthetase (NAGS)
- Carbamyl phosphate synthetase (CPS)
- Argininosuccinate synthetase (ASS)
- Ornithine transcarbamylase (OTC)
- Argininosuccinate lyase (ASL)
- Arginase (ARG) 1
- Infections, which can cause the condition to go out of control 2
From the Research
Hyperammonemia is primarily caused by conditions that impair the body's ability to process ammonia, including liver diseases, genetic disorders of the urea cycle, and certain medications, as evident in the most recent study 3. The most common causes of hyperammonemia include:
- Liver diseases such as cirrhosis, hepatitis, and liver failure, which prevent proper ammonia detoxification
- Genetic disorders of the urea cycle, such as ornithine transcarbamylase deficiency, which disrupt the conversion of ammonia to urea
- Certain medications, including valproic acid, carbamazepine, and some chemotherapeutics, that can trigger hyperammonemia Other causes of hyperammonemia include:
- Portosystemic shunts that allow blood to bypass the liver
- Excessive protein intake
- Gastrointestinal bleeding, where blood proteins are broken down by gut bacteria
- Severe infections Treatment of hyperammonemia depends on the underlying cause, but often includes:
- Reducing protein intake
- Administering lactulose or rifaximin to reduce intestinal ammonia production
- Hemodialysis in severe cases
- Specific dietary restrictions and medications, such as sodium phenylbutyrate or sodium benzoate, for genetic disorders to provide alternative pathways for nitrogen excretion, as reported in 4 and 5. It is essential to suspect urea cycle disorders, such as ornithine transcarbamylase deficiency, in adult patients presenting with marked hyperammonemia without liver cirrhosis, and to promptly initiate hemodialysis to remove ammonia, regardless of the causative disease, as emphasized in 3.