Check ammonia levels immediately
in neonates with unexplained:

Poor feeding
or vomiting

Alteration in consciousness

Encephalopathy

Respiratory Distress
Delayed recognition and treatment of hyperammonemia
may result in irreversible neurological damage or death.
Neurological Presentations
- Altered level of consciousness (from somnolence to lethargy to coma)—mimicking encephalitis or drug intoxication
- Acute encephalopathy, cerebral edema
- Seizures (generally not isolated but with altered level of consciousness)
- Respiratory distress, tachypnea, hyperventilation, respiratory alkalosis
- Sepsis-like picture (including temperature instability, hypo- or hyperthermia)
- Hypotonia
- Neurologic posturing
- Hepatomegaly
- Irritability
- Multiorgan failure
- Peripheral circulatory failure
Gastrointestinal Presentations
- Progressive poor appetite or poor feeding
- Vomiting
Go beyond sepsis
Think inborn errors of metabolism
Initial nonspecific symptoms of
hyperammonemia may mimic sepsis.
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.
- Confirmed septicemia does not exclude a primary hyperammonemic defect, such as a UCD.
- Ammonia is not part of a routine sepsis lab workup.
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.
IEMs that cause hyperammonemia
- Urea cycle disorders
- Transport defects of urea cycle intermediaries
- Organic acidemias
- Fatty acid oxidation disorders
- Ornithine aminotransferase deficiency (neonate)
- Pyruvate decarboxylase deficiency
- Liver failure secondary to IEM
Non-IEMs that cause hyperammonemia
- Severe sepsis
- Liver failure
- Intra- and extra-hepatic shunting, including transient hyperammonemia of the newborn (THAN)
- Herpes simplex infection
- Infection with urea-splitting organisms