From the Guidelines
Hyperammonemia is a life-threatening condition characterized by excessive accumulation of ammonia in the blood, leading to moderate to severe neurological impairment and cerebral edema.
Key Points
- Hyperammonemia can result from various causes, including inborn errors of metabolism, such as urea cycle disorders (UCDs) and organic acidemias, as well as liver and kidney diseases 1.
- The condition is defined as blood ammonia concentrations >100 µmol/l (170 µg/dl) in neonates or ≥50 µmol/l (85 µg/dl) in term infants, children, and adolescents 1.
- Symptoms of hyperammonemia vary depending on the age of the patient and the underlying cause, but can include lethargy, loss of appetite, vomiting, hypotonia, seizures, and coma 1.
- The primary differential diagnosis of hyperammonemia in infants and children relates to inborn errors of metabolism, including UCDs and organic acidemias 1.
- Management of hyperammonemia is challenging and requires prompt identification and treatment, including non-kidney replacement therapy (NKRT) and kidney replacement therapy (KRT) 1.
Treatment Options
- KRT includes peritoneal dialysis (PD), haemodialysis (HD), and continuous kidney replacement therapy (CKRT) 1.
- The success rates for each modality vary, with 65% for PD, 100% for intermittent HD, and 60% for CKRT 1.
Important Considerations
- Early onset hyperammonemia presents in neonates within the first few days of life and can be life-threatening if left untreated 1.
- Late-onset hyperammonemia in children, adolescents, or adults can result from a partial or mild deficiency in a urea cycle enzyme that is exacerbated by certain stressors 1.
- The clinical features of an acute hyperammonaemic episode depend on the age of the patient and the cause of the elevation in plasma ammonia levels 1.
From the Research
Definition and Causes of Hyperammonemia
- Hyperammonemia is defined as an excessive accumulation of ammonia in the blood, typically above 100 µmol/L in neonates or above 50 µmol/L in term infants, children, and adolescents 2.
- It can be caused by inherited metabolic diseases, as well as acquired disorders such as liver failure, portosystemic shunting, gastrointestinal hemorrhage, and certain drugs 2, 3.
- Hyperammonemia can also occur due to increased production or impaired detoxification of ammonia, and can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology 4.
Clinical Significance and Symptoms
- Hyperammonemia is a medical emergency that can progress to cerebral edema, seizures, coma, and death if left untreated 3.
- Patients with hyperammonemia often experience life-threatening neuropsychiatric symptoms, especially newborns 2.
- The main prognostic factors for hyperammonemia are the duration of the hyperammonemic coma and the extent of ammonia accumulation, regardless of the underlying cause 4.
Pathophysiology and Mechanisms
- The pathophysiology of hyperammonemia involves the toxicity of ammonia to the brain, which can be caused by an increased flux through the serotonin pathway, involvement of NMDA receptors, glutamate, NO, and cGMP 5.
- The gamma-glutamyl cycle, which is responsible for glutathione formation, plays a crucial role in the development of hyperammonemia 5.
- Hyperammonemia can also affect axonal development and energy metabolism in the developing brain, potentially leading to mental retardation 5.
Diagnosis and Treatment
- Early recognition and treatment of hyperammonemia are essential to prevent irreversible brain damage 4, 3.
- Measurement of plasma ammonia is recommended for patients with acute, unexplained, altered mental status, but its sensitivity and specificity are limited 3.
- A framework for investigating the acute non-cirrhotic causes of hyperammonemia can assist clinicians in managing these challenging cases 3.