Check ammonia levels immediately
in neonates with unexplained:

child in high chair not wanting to eat

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
REFERENCES