What are the causes of Hyperammonemia (elevated ammonia levels)?

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)

The causes of Hyperammonemia (elevated ammonia levels) include:

• Urea cycle disorders due to decreased activity of certain enzymes, such as:
  • N-acetylglutamate synthetase (NAGS)
  • Carbamyl phosphate synthetase (CPS)
  • Argininosuccinate synthetase (ASS)
  • Ornithine transcarbamylase (OTC)
  • Argininosuccinate lyase (ASL)
  • Arginase (ARG) 1 1

From the Research

Hyperammonemia is almost always caused by severe liver failure, and other nonhepatic causes such as drugs, infection, and inborn errors of metabolism may be overlooked, according to the most recent study 2. The causes of hyperammonemia can be multifactorial, but the most common cause is liver dysfunction, particularly in patients with severe liver failure. Other causes include urea cycle disorders, certain medications, and inborn errors of metabolism.

• Liver dysfunction: Liver failure can lead to impaired ammonia detoxification, resulting in elevated ammonia levels in the blood.
• Urea cycle disorders: These are genetic disorders that affect the body's ability to remove ammonia from the blood.
• Medications: Certain medications, such as valproic acid, can impair ammonia metabolism and lead to hyperammonemia.
• Inborn errors of metabolism: These are genetic disorders that affect the body's ability to metabolize certain substances, leading to elevated ammonia levels.
• Other causes: Other causes of hyperammonemia include intense skeletal muscle activity, as seen in a case report where a patient developed severe hyperammonemia after intense muscle activity 3. It is essential to identify the underlying cause of hyperammonemia to provide appropriate treatment and prevent long-term neurological damage.
• Regular monitoring of ammonia levels, neurological status, and electrolyte balance is crucial during treatment.
• Treatment may involve reducing ammonia levels through medication and dietary modifications, such as protein restriction and oral ammonia scavengers.
• In severe cases, hemodialysis may be necessary to remove excess ammonia from the blood. The most recent study 2 highlights the importance of recognizing and treating hyperammonemia promptly to prevent progressive neurological damage and improve outcomes for patients.
• Any coma of unclear cause should prompt urgent measurement of ammonia, and severe elevations warrant immediate protective measures and treatment.
• The study also emphasizes the need for increased awareness of hyperammonemia and its causes, particularly nonhepatic causes, to improve clinical management and outcomes.