Hyperammonemia acquired

Symptoms of hereditary hyperammonemia include many of the neurologic manifestations of acquired hyperammonemia, but they are seen mainly in infants and frequently lead to mental retardation. 

Acquired hyperammonemia Liver disease is a common cause of hyperammonemia in adults. It may be a result of an acute po cess, for example, viral hepatitis, ischemia, or hepatotoxins. Cirrhosis of the liver caused by alcoholism, hepatitis, or biiary obstruction may result in formation of collateral circulation around the liver. As a result, portal blood is shunted directly rto the systemic circulation and does not have access to the ter. The detoxification of ammonia (that is, its conversion to urea) is, therefore, severely impaired, leading to elevated levels of cicu lating ammonia. 

Because the CNS is sensitive to ammonia, its metabolism in the brain and the neurotoxicity associated with hyperammonia and hepatic encephalopathy (the proximate source of damage in the latter is also ammonia) is reviewed here. Hepatic encephalopathy (HE) or congenital and acquired hyperammonemia result in excessive ammonia accumulation within the CNS. The condition is due... 

Animal and human studies have shown that an elevated concentration of ammonia (hyperammonemia) exerts toxic effects on the central nervous system. There are several causes, both inherited and acquired, of hyperammonemia. The inherited deficiencies of urea cycle enzymes are the major cause of hyperammonemia in infants. The two major inherited disorders are those involving the metabolism of the dibasic amino acids lysine and ornithine and those involving the metabolism of organic acids, such as propionic acid, methylmalonic acid, isovaleric acid, and others (see Chapter 55). 

The acquired causes of hyperammonemia are advanced liver disease and renal failure. Severe or chronic liver failure (as occurs in fiilminant hepatitis and cirrhosis, respectively) leads to a significant impairment of normal ammonia metabolism. Reye s syndrome, which is primarily a central nervous system disorder with minor hepatic dysfunction, is also associated with hyperammonemia. Hepatic en-... 

Hyperammonemia resulting from any of the enzymatic disorders of the biosynthesis of urea, must be distinguished from other conditions in which plasma ammonia is raised, sometimes sufficiently so to cause clinical manifestation. Severe liver disease as a primary cause of acquired hyperammonemia may be excluded from consideration since it is readily distinguishable from urea cycle defects. However, there are a number of other conditions described with hyperammonia as a prime manifestation, which because they show some clinical and biochemical similarity to hereditary enzyme defects of the urea cycle, have been claimed to be urea cycle disorders. 

Hyperammonemia may also result from congenital or acquired causes that are not related to inherited metabolic diseases. Examples of congenital causes include malformations such as portosystemic shunts, extrahepatic portal vein obstructions, and cirrhosis with portal hypertension. Transient hyperammonemia of the newborn (THAN) is typically identified in premature infants and does not appear to have a neurologic effect on those asymptomatic preterm infants [11]. Liver failure may also result in fulminant hyperammonemia. In severe liver failure, all of the enzymes expressed in the liver are deficient, resulting in complete impairment of the urea cycle as well as a deficiency of other important liver-specific enzymes snch as the glycine cleavage enzyme. 

---