Hyperammonemia due to Organic Acidemias

Hyperammonemia refers to a wide spectrum of metabolic conditions characterized by raised levels of ammonia. Hyperammonemia may be induced when ammonia detoxification is affected.

Detoxification of ammonia is mainly accomplished by the urea cycle in hepatocytes.

Ammonia is converted to urea, and urea is then excreted via the kidneys.

Inhibition of the urea cycle may be the result of intermediary metabolites that accumulate due to enzymatic defects in other pathways. The most relevant group of disorders in this respect is that of organic acidemias, such as propionic, methylmalonic and isovaleric acidaemia (1).

Propionic, methylmalonic and isovaleric acidaemia become clinically apparent during the neonatal period, particularly within the first days of life. Common features of these acidaemias are hyperammonaemia, acidosis, neutropenia and thrombocytopenia. Patients may develop symptoms, such as tachypnea, vomiting and coma (2).

Propionic, methylmalonic and isovaleric acidaemias are rare genetic disorders. Prevalence of propionic acidemia ranges from 1 to 9 cases per 1.000.000 (3). Prevalence of methylmalonic and isovaleric acidemia is between 1 and 9 cases per 100.000 (4), (5), (6).

Diagnosis is performed by specialized physicians. Diagnosis of propionic, methylmalonic and isovaleric acidaemia may require examinations, such as blood and urine tests (7). Physicians evaluate the condition of patients. Treatment decisions are made by specialized physicians.