Check for ammonia immediately in infants, children, or adults with unexplained:1,2,3,4,5

  • GI presentations
    (vomiting, protein aversion)
  • Alteration in
  • Encephalopathy
  • Movement disorders
    or seizures
  • Learning problems or
    developmental delay
  • Psychiatric

Delayed recognition and treatment of hyperammonemia may result in irreversible neurological damage or death.2

Learn more about:

  • Neurological Presentations
    • Confusion,1,6 lethargy, dizziness1
    • Migraine-like headaches1
    • Tremor, ataxia, dysarthria1
    • Intellectual/learning disabilities,1 neurodevelopmental delay1,7
    • Seizures1
    • Hemiplegia8
    • Coma9
  • Gastrointestinal Presentations
    • Abdominal pain,1 nausea,6,7 vomiting1,7
    • Protein aversion, self-selected low-protein diet1
    • Failure to thrive1
    • Hepatomegaly, elevated liver enzymes1
  • Psychiatric Presentations
    • Behavioral changes, mood alteration, hyperactivity, aggressiveness,1 combativeness6
    • Delusions, psychosis10
    • Sleep disorders11

Differential diagnosis in infants, children, and adults

Hyperammonemia in infants, children, and adults can be caused by many different diseases and disorders. Regardless of hyperammonemia cause, in any patient with nonspecific, unexplained neurological symptoms:

Go beyond liver disease

Think inborn errors of metabolism

In older individuals, hyperammonemia is often the consequence of
a diseased liver.12

Even in patients with known hepatic disease, clinicians should consider other reasons for their hyperammonemia, such as late-onset urea cycle disorder (UCDs) or other inborn errors of metabolism.13 UCDs affect neonates, but 69% of people with UCDs first present with symptoms later in life.3

If high plasma ammonia levels are detected in an infant, child, or adult, differential diagnosis can rule out many different disorders that may be causing the hyperammonemia .14

Inborn errors of metabolism that may cause hyperammonemia

  • Urea cycle disorders (UCDs)14
  • Organic acidemias, such as propionic acidemia (PA) or methylmalonic acidemia (MMA)15
  • Tyrosinemia type 114
  • Galactosemia14
  • Mitochondrial disorders14
  • Fatty acid oxidation disorders14
  • Citrin deficiency leading to citrullinemia type II (CTLN2)14

When to Suspect a Late-Onset UCD - Key Questions to Consider

Nonspecific symptoms and non-related illnesses can make it difficult to recognize late-onset UCDs. Click below for key investigative questions that can be part of a detailed patient/family history when a late-onset UCD is suspected.


1. 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.

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

3. Batshaw ML, Tuchman M, Summar M, Seminara J. A longitudinal study of urea cycle disorders. Mol Genet Metab 2014;113:127-130.

4. Al Kaabi EH, El-Hattab AW. N-acetylglutamate synthase deficiency: Novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra. Mol Genet Metab Rep 2016;8:94-98

5. Kolker S, Cazorla AG, Valayannopoulos V, Lund AM, Burlina AB, Sykut-Cegielska J, Wijburg W, Teles EL et al. The phenotypic spectrum of organic acidemias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis 2015;38:1041-1057.

6. Ah Mew N, Caldovic L. N-acetylglutamate synthase deficiency: an insight into the genetics, epidemiology, pathophysiology, and treatment. Appl Clin Gen 2011;4:127-135.

7. Cartagena A, Prasad AN, Rupar CA, Strong M, Tuchman M, Ah Mew N, Prasad C. Recurrent encephalopathy: NAGS (N-acetylglutamate synthase) deficiency in adults. Can J Neurol Sci 2013;40:3-9.

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

9. Caldovic L, Morizono H, Tuchman M. Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene. Hum Mutat 2007;28:754-759.

10. Summar ML, Tuchman M. Proceedings of a consensus conference for the management of patients with urea cycle disorders. J Pediatr 2001;138(1 Suppl):S6-S10.

11. 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. Updated June 22, 2017. Accessed September 22, 2017.

12. Roth K. Genetics of hyperammonemia. eMedicine/Medscape. Updated Mar 29, 2016. Available at: Accessed September 7, 2017.

13. LaBuzetta JN, Yao JZ, Bourque DL, Zivin J. Adult nonhepatic hyperammonemia: A case report and differential diagnosis. Am J Med 2010;123(10):885-891. 13. 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.

14. 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.

15. Haberle J, Burlina A, Chakrapani A, Dixon M, Karall D, Lindner M, Mandel H, Martinelli D, Pintos-Morell G, Santer R, Skouma A, Servais A, Tal G, Rubio V, Huemer M, Dionisi-Vici C. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. 2019;1-39.