Can Hyperammonemia Cause Tremor?
Yes, tremors are a well-documented neurological manifestation of hyperammonemia and should be recognized as part of the clinical spectrum of ammonia-induced neurotoxicity. 1, 2
Neurological Manifestations of Hyperammonemia
Tremors occur alongside other movement disorders in hyperammonemia, specifically appearing with ataxia and dysarthria as part of the neurological symptom complex. 1, 2
Complete Neurological Symptom Profile
The neurological manifestations of hyperammonemia include:
- Tremors, ataxia, and dysarthria - these movement disorders typically present together as ammonia levels rise 1, 2
- Early symptoms: confusion, lethargy, and dizziness 1
- Progressive symptoms: hypotonia, migraine-like headache, learning disabilities, neurodevelopmental delay 1
- Severe manifestations: seizures, hemiplegia, coma 1
Pathophysiological Mechanism
Ammonia crosses the blood-brain barrier and is metabolized to glutamine by astrocytes, causing increased extracellular potassium and glutamine levels that lead to increased intracellular osmolality and cerebral edema. 1, 2
- This results in neuronal damage and release of inflammatory cytokines, which manifests clinically as the various neurological symptoms including tremors 1, 2
- The severity of neurological manifestations correlates with both the magnitude and duration of hyperammonemia 3, 4
Clinical Severity Thresholds
Hyperammonemia is defined as >100 μmol/L (170 μg/dL) in neonates or ≥50 μmol/L (85 μg/dL) in term infants, children, and adults. 5, 2
- Normal blood ammonia concentrations are ≤35 μmol/L (≤60 μg/dL) 5, 2
- Levels >200 μmol/L (341 μg/dL) are associated with poor neurological outcomes 5, 2
Age-Dependent Presentation Patterns
In neonates, tremors appear later in the clinical course after initial symptoms of lethargy, poor feeding, and vomiting progress to hypotonia and hyperventilation. 1, 5
In older patients with partial enzyme deficiencies, tremors may present episodically, triggered by metabolic stressors such as illness or increased protein intake. 5
Common Etiologies to Consider
When tremors are identified in the context of hyperammonemia, consider:
- Primary causes: Urea cycle disorders (UCDs) due to congenital enzyme deficiencies, with ornithine transcarbamylase (OTC) deficiency being the most common 5, 2
- Secondary causes: Organic acidemias (methylmalonic acidemia, propionic acidemia), valproic acid therapy, acute kidney injury, or liver disease 5, 2
Critical Clinical Pitfall
Do not dismiss tremors as a benign finding in patients with altered mental status - measure ammonia levels immediately, as tremors represent a significant neurological manifestation that warrants urgent evaluation and treatment. 1, 2 The presence of respiratory alkalosis alongside tremors is an important early clue that distinguishes hyperammonemia from other causes of encephalopathy 5.