Ammonia (NH3+) and its associated acid ammonium (NH4+) result from the catabolism of amino acids (AA). For simplicity, in this case report the term ammonia refers to both forms. In healthy individuals, the main source of ammonia is digestive from intestinal bacterial degradation of proteins and urea. Catabolism of AA continually produces ammonia in human organs. The kidney is another main source, which produces ammonia in the proximal tubular cells in order to buffer H+ in urine. Elimination of ammonia in a healthy individual takes place in the liver, where it is transformed into urea by periportal hepatocytes (the urea cycle). Urea, a nontoxic molecule, is subsequently eliminated in the urine and colon. A second key actor of ammonia metabolism is glutamine synthase (GS), which produces glutamine by incorporating ammonia in glutamate. This enzyme is present in periportal hepatocytes and prevents the release of residual ammonia into the systemic circulation. Produced glutamine is then transported to the small intestine, where ammonia is released, and then carried back to the liver via the portal system. GS is also expressed in muscles, kidneys, and astrocytes acting as an initial adaptive mechanism in case of hyperammonemia. Finally, the kidney can increase ammonia excretion in urine from 30% up to 70% [
1‐
3]. Ammonia gets access to the brain through passive diffusion and mediated transport. It is then combined with glutamate by astrocytes to produce glutamine, which is provided to neurons, reversed back to glutamate and then released as a neurotransmitter. When present in an excessive amount, ammonia has a selective neurotoxicity. Clinical manifestations range from irritability to seizure, coma, cerebral herniation, and death [
2]. Hosting the urea cycle, the liver plays an essential role in ammonia detoxification; thus, up to 90% of cases of hyperammonemia are related to hepatic diseases. Apart from hepatic dysfunction, two mechanisms may lead to ammonia excess: increased production and decreased metabolism (Table
1). Ammonia production is raised in cases of exaggerated protein supply (enteral or parenteral), muscle protein catabolism (seizure, trauma, malnutrition), urinary tract infection with urease producing bacteria, and hemato-oncological disorders. Ammonia elimination is altered in cases of inborn errors of metabolism, by medication interfering with urea cycle (for example, valproate), and by portosystemic shunting. Constitutional defects of ammonia metabolism may only be apparent in adulthood, following a precipitating event [
3].
Table 1
Mechanism leading to nonhepatic hyperammonemia: increased production and decreased metabolism
Excessive protein supply (enteral or parenteral) | Portosystemic shunting |
Muscles catabolism: cachexia, starvation, seizure | Medications interfering with urea cycle: valproic acid, carbamazepine, salicylate, glycine, ribavirin |
Urease producing bacteria urinary tract infections: Proteus mirabilis, Klebsiella species, Escherichia coli, Morganella morganii, Providencia rettgeri, diphtheroids | Inborn error of metabolism: inherited defects of the urea cycle, amino acid transporters, fatty acid oxidation, organic acid disorders |
Hematological malignancies: multiple myeloma, leukemia | |
Electroencephalography (EEG) has a well-recognized role in the evaluation of altered consciousness states. It is a diagnostic and monitoring tool, providing prognostic information. With worsening of metabolic encephalopathies, gradual EEG progression is observed, similar to changes described in drug-induced coma. As the amplitude increases, the dominant EEG frequency declines and the length of flat periods increases toward a completely isoelectric trace [
4]. The burst suppression pattern consists of alternative periods of slow waves with high amplitude (the burst phase) and periods of marked activity depression (the suppression phase). It is associated with profound coma of various etiologies (cerebral anoxia, hypothermia, anesthesia, drugs intoxications) [
5]. To the best of our knowledge, we report here the first case of an adult with hyperammonemic coma presenting with burst suppression on admission EEG.