What is the cause of Argininosuccinate lyase deficiency?
Alterations in the ASL gene lead to low levels of functional argininosuccinate lyase, which is needed to break down nitrogen in the body. Failure to properly break down nitrogen leads to the abnormal accumulation of nitrogen, in the form of ammonia, in the blood (hyperammonemia).
What does argininosuccinate synthase do?
Argininosuccinate synthase plays an important role as the rate-limiting step in providing arginine for an assortment of metabolic processes, both catabolic and anabolic. Thus, the metabolic pathways in which argininosuccinate synthase participates are linked to the varied uses of the amino acid arginine.
Can Citrullinemia be cured?
Liver transplantation is possible and, if done early in life, may eliminate the symptoms of the disorder. Left untreated, people with citrullinemia will build up very high levels of ammonia in the blood that can lead to brain damage and eventually death.
Why is arginine given in Citrullinemia?
Arginine, sodium benzoate and sodium phenylacetate help to remove ammonia from the blood. Dialysis may be used to remove ammonia from the blood when it reaches critical levels.
How is arginase deficiency treated?
Treatment is focused on lowering arginine levels and preventing hyperammonemia. People with arginase deficiency are generally placed on a very low-protein diet with the help of a registered metabolic dietitian . They may be prescribed certain medications called nitrogen-scavenging drugs.
What are the disorders of urea cycle?
Primary urea cycle disorders (UCDs) include carbamoyl phosphate synthase (CPS) deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinate synthetase deficiency (citrullinemia), argininosuccinate lyase deficiency (argininosuccinic aciduria), and arginase deficiency (argininemia).
What is Argininosuccinate lyase deficiency?
Defect: Argininosuccinate Lyase (ASL) Deficiency, also known as Argininosuccinic Aciduria (AA), is the result of a mutated or deficient argininosuccinate lyase enzyme. This defective or deficient enzyme leads to inadequate ureagenesis, accumulation of argininosuccinic acid, and deficient endogenous arginine production.
Is Citrullinemia common?
Type I citrullinemia is the most common form of the disorder, affecting about 1 in 57,000 people worldwide. Type II citrullinemia is found primarily in the Japanese population, where it occurs in an estimated 1 in 100,000 to 230,000 individuals.
Why ammonia is toxic to brain?
When excessive amounts of ammonia enter the central nervous system, the brain’s defences are severely challenged. – A complex molecular chain reaction is triggered when the brain is exposed to excessive levels of ammonia. We have found that ammonia short-circuits the transport of potassium into the brain’s glial cells.
How common is arginase deficiency?
Affected Populations Arginase-1 deficiency has been estimated to occur in approximately 1 in 300,000-1,000,000 births. Arginase-1 deficiency is among the least common of all the disorders of the urea cycle.
How is argininosuccinate synthetase deficiency ( ASD ) treated?
Treatment of Argininosuccinate Synthetase Deficiency ASD patients are treated in much the same ways as for other neonatal UCDs in that protein intake must me highly regulated and the hyperammonemia must be controlled. Hemodialysis is the only effective means to rapidly lower serum ammonia levels in these patients.
Which is the best treatment for argininosuccinate lyase deficiency?
Hemodialysis, if available, reduces the blood ammonia levels more efficiently and quickly. Long-term therapy should involve a low-protein diet and arginine supplementation.
How to treat argininosuccinic aciduria in the long term?
Long-term management includes dietary restriction of protein and supplementation with arginine. Acute crises may be treated by discontinuing oral protein intake, supplementing oral intake with intravenous lipids and/or glucose, and use of intravenous arginine and nitrogen scavenging therapy.
How many mutations are there in the argininosuccinate synthetase gene?
There are at least 22 known mutations in the AS gene that result in argininosuccinate synthetase deficiency (ASD). Mutations include missense, nonsense and exon deletions. The frequency of ASD is approximately 1 per 57,000 live births.
