Check for ammonia immediately in
infants, children, or adults with unexplained:

GI presentations

Alterations in consciousness

Encephalopathy

Learning problems or developmental delays

Psychiatric presentations

Movement disorders
or seizures

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

Neurological Presentations

Confusion, lethargy, dizziness

Migraine-like headaches

Tremor, ataxia, dysarthria

Intellectual/learning disabilities, neurodevelopmental delay

Seizures

Hemiplegia

Coma

Psychiatric Presentations

Behavioral changes, mood alteration, hyperactivity, aggressiveness, combativeness
Delusions, psychosis
Sleep disorders

Gastrointestinal Presentations

Abdominal pain, nausea, vomiting
Protein aversion, self-selected low-protein diet
Failure to thrive
Hepatomegaly, elevated liver enzymes

Go beyond liver disease

Think inborn errors of metabolism

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

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. UCDs affect neonates, but 69% of people with UCDs first present with symptoms later in life.
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.

Inborn errors of metabolism that may cause hyperammonemia

  • Urea cycle disorders (UCDs)
  • Organic acidemias, such as propionic acidemia (PA) or methylmalonic acidemia (MMA)
  • Tyrosinemia type 1
    Galactosemia
  • Mitochondrial disorders
  • Fatty acid oxidation disorders
  • Citrin deficiency leading to citrullinemia type II (CTLN2)

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.