Why is there no hyperammonemia in arginase deficiency?

The severe hyperammonemia observed in other urea cycle defects is rarely observed in patients with arginase deficiency for at least 2 identifiable reasons. The first reason is that formed arginine, which contains 2 waste nitrogen molecules, can be released from the hepatocyte and excreted in urine.

Which of the following is a possible consequence of an arginase deficiency?

If untreated, arginase deficiency usually progresses to severe spasticity, loss of ambulation, complete loss of bowel and bladder control, and severe intellectual disability. Seizures are common and are usually controlled easily.

Which enzyme defect causes hyperammonemia?

Hyperammonemia is mild in arginase deficiency, and the associated neuronal damage is due to elevated levels of arginine. Other enzymatic defects causing hyperammonemia are associated with additional metabolic abnormalities. Ketosis and acidosis are associated with organic acidemias such as isovaleric acidemia.

What deficiency causes ammonia?

Carbamoyl phosphate synthetase I deficiency is an inherited disorder that causes ammonia to accumulate in the blood (hyperammonemia). Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high.

What happens in arginase deficiency?

The lack of the arginase enzyme results in excessive accumulation of nitrogen, in the form of ammonia (hyperammonemia), in the blood and arginine (hyperarginemia) in the blood and cerebrospinal fluid. Untreated children may exhibit seizures, spasticity, short stature and intellectual disability.

What is the function of arginase in urea cycle?

The ureohydrolase arginase is a manganese-containing enzyme that catalyzes the final step in the urea cycle to dispose of toxic ammonia by converting l-arginine to l-ornithine and urea (229). Its importance in this cycle has long been recognized.

What is the function of arginase enzyme?

The arginases catalyze the divalent cation dependent hydrolysis of L-arginine to produce L-ornithine and urea. Although traditionally considered in terms of its role as the final enzyme of the urea cycle, the enzyme is found in a variety of nonhepatic tissues.

What is ammonia deficiency?

Ornithine transcarbamylase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

What causes arginase deficiency?

Arginase-1 deficiency is inherited as an autosomal recessive genetic disorder and is caused by mutations in the ARG1 gene. Mutations in the ARG1 gene result in production of an abnormal arginase enzyme.

Why is arginase important?

Arginase-Ornithine Pathway. Activity of arginase has two primary physiological functions: 1) detoxification of ammonia in the urea cycle and 2) production of ornithine needed for the synthesis of proline and polyamines (FIGURE 2) (229).

What happens to an infant with arginase 1 deficiency?

Most infants with arginase-1 deficiency do not exhibit any symptoms during the first few months to a year of life. Infants with arginase-1 deficiency infrequently experience severe hyperammonemia or hyperammonemic coma, which are characteristic of the other urea cycle disorders.

How does arginase-1 deficiency affect the urea cycle?

Arginase-1 deficiency is inherited as an autosomal recessive genetic disorder. The urea cycle disorders are a group of rare disorders affecting the urea cycle, a series of biochemical processes in which nitrogen is converted into urea and removed from the body through the urine.

How often does arginase deficiency occur in the United States?

Arginase deficiency has been estimated to occur in approximately 1 in 300,000-1,000,000 births. Arginase deficiency is among the least common of all the disorders of the urea cycle. The estimated frequency of urea cycle disorders collectively is one in 30,000.

Can a hyperammonemic baby have metabolic acidosis?

The presence of respiratory alkalosis in a sick, hyperammonemic neonate or infant is an indicator of an underlying urea cycle defect since it is an uncommon finding in an ill neonate secondary to other causes. Hyperammonemia with metabolic acidosis is more likely to be due to an organic acid disorder in which the hyperammonemia is secondary.