Check ammonia levels immediately in neonates with unexplained:1,2

  • Poor feeding
    or vomiting
  • Alteration in
    consciousness
  • Encephalopathy
  • Respiratory
    distress
  • Sepsis-like
    symptoms

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

Learn More about:

  • Neurological Presentations
    • Altered level of consciousness (from somnolence to lethargy to coma)—mimicking encephalitis or drug intoxication
    • Acute encephalopathy,1 cerebral edema3
    • Seizures (generally not isolated but with altered level of consciousness1,4) 
    • Respiratory distress,1 tachypnea,3 hyperventilation,1 respiratory alkalosis2
    • Sepsis-like picture1,5 (including temperature instability,1 hypo- or hyperthermia2)
    • Hypotonia5
    • Neurologic posturing6
    • Hepatomegaly3
    • Irritability3
    • Multiorgan failure1
    • Peripheral circulatory failure1
  • Gastrointestinal Presentations
    • Progressive poor appetite1 or poor feeding2,4
    • Vomiting1,4

Neonatal differential diagnosis

Neonatal presentations of hyperammonemia can be caused by many different diseases and disorders. Regardless of cause, in any neonate with nonspecific, unexplained neurological symptoms:

Check
Ammonia
Call a
Metabolic
Geneticist

Go beyond sepsis

Think inborn errors of metabolism

Initial nonspecific symptoms of hyperammonemia may mimic sepsis.7

But be aware that:

  • Newborns who develop severe hyperammonemia after 24 hours of age usually have a urea cycle disorder (UCD) or an organic acidemia—both inborn errors of metabolism (IEMs). Although sepsis is often considered first, symptoms in a full-term infant with no specific risk factors strongly suggest a metabolic disorder.8
  • Confirmed septicemia does not exclude a primary hyperammonemic defect, such as a UCD.2
  • Ammonia is not part of a routine sepsis lab workup.9,10

Other causes of hyperammonemia in neonates

In addition to urea cycle disorders and organic acidemias, a number of other IEMs can cause hyperammonemia. Hyperammonemia can also be caused by non-IEM-related diseases and disorders. A differential diagnosis in neonates should consider all causes.11

IEMs that cause hyperammonemia11

  • Urea cycle disorders
  • Transport defects of urea cycle intermediaries
  • Organic acidemias
  • Fatty acid oxidation disorders
  • Ornithine aminotransferase deficiency
    (neonatal form)
  • Pyruvate decarboxylase deficiency
  • Liver failure secondary to IEM

Non-IEM-related hyperammonemia11

  • Severe sepsis8,11
  • Liver failure
  • Intra- and extra-hepatic shunting,
    including transient hyperammonemia of the newborn (THAN)
  • Herpes simplex infection8,11
  • Infection with urea-splitting organisms

Hyperammonemia and Neonatal UCDs - Case Summaries

Full-term neonate with symptoms of hyperammonemia starting on day 2

Full-term neonate with symptoms of hyperammonemia starting on day 3

References:
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. 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.

4. 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.

5. 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.

6. 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.

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

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

9. Maggio PM. Sepsis and septic shock. Merck Manual, Professional Version, 2017. Revised April 2016. Available at: http://www.merckmanuals.com/professional/critical-care-medicine/sepsis-and-septic-shock/sepsis-and-septic-shock#v928482. Accessed October 2, 2017.

10. Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr 2015;61:1-13.

11. Broomfield AA, Walter JH. Treatment of hyperammonemia in the newborn. A report. Willink Biochemical Genetics Unit, Royal Manchester Children’s Hospital. Eur Paediatr 2008;36-39.