Signs and symptoms of hyperammonemia
Clinical signs and symptoms of hyperammonemia are mainly neurological in origin. Yet symptoms are generally nonspecific and may suggest several diagnostic pathways. Given the potential risk of brain injury or death due to hyperammonemia, it’s critical to suspect and test for the condition—especially with any unexplained alteration in consciousness or encephalopathy.
Although there is some overlap, hyperammonemia symptoms can differ depending on the patient’s age
Common causes of hyperammonemia
The underlying causes of hyperammonemia can be diverse.
Some of the more common causes include:
Liver Failure
Hepatocyte destruction and reduced urea cycle enzyme function
Drug reactions
E.g., inhibition of the urea cycle by valproic acid
Hemolytic disease
Release of ammonia from red blood cells
Gastrointestinal bleeds
Hepatocyte destruction and reduced urea cycle enzyme function
Urea cycle disorders
Urea cycle disorders/Other inborn errors of metabolism
Regardless of the cause, hyperammonemia can be toxic to the central nervous system. Awareness is the first step to preventing possible irreversible brain damage or death.
Other causes and triggers of hyperammonemia
Hyperammonemia can be caused by many diseases and disorders. In patients who have an underlying metabolic disorder, medical events or other stressors can trigger a hyperammonemic crisis. This can occur in patients with milder disorders who have been functioning relatively normally – sometimes for decades.
Illness/Surgery
- Viral or bacterial infections (e.g., urinary tract, herpes simplex, gastrointestinal bacterial overgrowth)
- Fever
- Vomiting
- Gastrointestinal or internal bleeding
- Recent surgery (e.g., lung or bone marrow transplant, portosystemic shunts, bariatric surgery leading to malabsorption, nutritional disruption, and rapid weight loss)
- Hepatic encephalopathy caused by advanced liver disease
- Vascular bypass of the liver
Other experiences that stress the body
- Periods of rapid growth (e.g., late infancy, young school-aged child, puberty)
- Prolonged or intense physical exercise, such as bodybuilding
- Peripartum period stressors
Limited or excess dietary protein
- Unusual protein load (e.g., barbecue or parenteral nutrition)
- Decreased energy or protein intake (e.g., fasting pre-surgery, self-selected low-protein diet)
Medications
- Valproate
- Chemotherapy drugs, such as cyclophosphamide
- High-dose glucocorticoids
Salicylic acid or aspirin (e.g., use in children during viral illness, resulting in Reye syndrome)