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.1

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Be aware of the signs and symptoms of hyperammonemia. Learn about caregivers’ and patients’ experiences that underscore the importance of suspecting and testing for hyperammonemia.

HYPERAMMONEMIA SYMPTOMS VIDEO

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Although there is some overlap, hyperammonemia symptoms can differ depending on the patient's age:

Review hyperammonemia
symptoms in neonates Review hyperammonemia symptoms
in infants, children, and adults

Common causes of hyperammonemia

The underlying causes of hyperammonemia can be diverse. Some of the more common causes include2:

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

Increased ammonia generation due to microbial catabolism of hemoglobin

Urea cycle disorders/Other inborn
errors of metabolism3,4

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.5

Illness/Surgery

  • Viral or bacterial infections (e.g., urinary tract, herpes simplex, gastrointestinal bacterial overgrowth)6,7,8
  • Fever6
  • Vomiting6
  • Gastrointestinal or internal bleeding6
  • Recent surgery (e.g., lung or bone marrow transplant, portosystemic shunts, bariatric surgery leading to malabsorption, nutritional disruption, and rapid weight loss)5,7
  • Hepatic encephalopathy caused by advanced liver disease8
  • Vascular bypass of the liver8

Limited or excess dietary protein

  • Unusual protein load (e.g., barbecue or parenteral nutrition)6
  • Decreased energy or protein intake (e.g., fasting pre-surgery, self-selected low-protein diet)6

Medications

  • Valproate6
  • Chemotherapy drugs, such as cyclophosphamide6,8
  • High-dose glucocorticoids6
  • Salicylic acid or aspirin (e.g., use in children during viral illness, resulting in Reye syndrome)1,11

Other experiences that stress the body

  • Periods of rapid growth (e.g., late infancy, young school-aged child, puberty)9
  • Prolonged or intense physical exercise, such as bodybuilding6,12
  • Peripartum period stressors10

References:

1. Haberle J. Clinical practice: The management of hyperammonemia. Eur J Pediatr 2011;170:21-34.

2. Orton DJ, Gifford JL, Seiden-Long I, Khan A, de Koning L. Critically high plasma ammonia in an adolescent girl. Clin Chem 2016;62(12):1565-1569.

3. Broomfield A, Grunewald S. How to use serum ammonia. Arch Dis Child Educ Pract Ed 2012;97:72–77.

4. Burton BK. Inborn errors of metabolism in infancy: A guide to diagnosis. Pediatrics 1998;102(6):E69.

5. Summar ML, Barr F, Dawling S, Smith W, Lee B, Singh RH, Rhead WJ, Sniderman King L, Christman BW. Unmasked adult-onset urea cycle disorders in the critical care setting. Crit Care Clin 2005;21:S1-S8.

6. Haberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Sanjurjo Crespo P, Santer R, Servais A, Valayannopoulos V, Lindner M, Rubio V,Dionisi-Vici C. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 2012;7:32.

7. LaBuzetta JN, Yao JZ, Bourque DL, Zivin J. Am J Med 2010;123(10):885-891.

8. Cesar Machado MC, da Silva FP. Hyperammonemia due to urea cycle disorders: A potentially fatal condition in the intensive care setting. J Intensive Care 2014;2:22.

9. Smith W, Kishnani PS, Lee B, Singh RH, Rhead WJ, Sniderman King L, Smith M, Summar M. Urea cycle disorders: Clinical presentation outside the newborn period. Crit Care Clin 2005;21:S9-S17.

10. Ah Mew N, Lanpher BC, Gropman A, Chapman KA, Simpson KL, Urea Cycle Disorders Consortium, Summar ML. Urea cycle disorders overview. In Pagon RA, Adam MP, Ardinger HH et al, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2017. http://www.ncbi.nlm.nih.gov/books/NBK1217. Updated June 22, 2017. Accessed September 22, 2017.

11.  N-acetylglutamate synthetase deficiency. National Organization for Rare Disorders. 2016. Available at: https://rarediseases.org/rare-diseases/n-acetylglutamate-synthetase-deficiency. Accessed September 11, 2017.

12.  Panlaqui OM, Tran K, Johns A, McGill J, White H. Acute hyperammonemic encephalopathy in adult onset ornithine transcarbamylase deficiency. Intensive Care Med 2008;34:1922-1924.

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