About arginase deficiency

What is arginase deficiency?

Arginase deficiency is a rare inherited disorder characterized by complete or partial lack of the enzyme arginase. Arginase is one of six enzymes that play a role in the breakdown and removal of nitrogen from the body, a process known as the urea cycle. 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. Arginase 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. Nitrogen is a waste product of protein metabolism. Failure to break down nitrogen results in the abnormal accumulation of nitrogen, in the form of ammonia, in the blood.

What are the symptoms for arginase deficiency?

Blood symptom was found in the arginase deficiency condition

Symptoms associated with arginase-1 deficiency differ from those associated with other disorders of the urea cycle. 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.

Affected children may experience a lag in growth between one and three years and may walk on their toes and develop progressive stiffness and lack of control of voluntary movements of the legs (spastic diplegia). Cognitive development slows or stops and if untreated, children develop severe spasticity, an inability to walk, loss of bowel and bladder control and severe intellectual disability.

Almost all affected children have growth deficiency and many also experience Seizures.

What are the causes for 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.

Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

What are the treatments for arginase deficiency?

Treatment should be coordinated by a metabolic specialist and is based on reducing plasma ammonia and arginine concentration, preventing excess ammonia from being formed, and reducing the amount of nitrogen in the diet.

Reduction of plasma ammonia concentration is accomplished by dialysis and several different methods are available. This should be used only when the high levels are producing severe symptoms.

The nitrogen scavenger drugs sodium phenylacetate and sodium benzoate provide an alternative pathway for removing excess nitrogen. Intravenous and oral forms of these medications are available (Ammonul). Phenylbutyrate (Buphenyl) has a less offensive odor than the other medications but is available as oral therapy only. Ravicti is a form of phenylbutyrate that is less irritating to the gastrointestinal track and easier to take.

Dietary restrictions in individuals with arginase-1 deficiency are aimed at limiting the amount of arginine and protein intake. Children with arginase-1 deficiency are placed on a low-protein, arginine-restricted diet supplemented by essential amino acids.

Seizures are treated with phenobarbital or carbamazepine. Valproic acid should be avoided, as it can increase blood ammonia levels.

Affected individuals should receive periodic blood tests to determine the levels of ammonia and arginine in the blood and to be sure that liver function is not impaired. Excessive levels of ammonia or arginine should be promptly treated.

Genetic counseling is recommended for affected individuals and their families.

What are the risk factors for arginase deficiency?

Arginase deficiency is an inherited metabolic disorder that makes the body unable to digest building blocks of protein. It causes amino acids arginine and amino acid to accumulate in the blood flow.

  • Arginase is one of six enzymes that have a significant role in removing and breaking down nitrogen from the body.
  • Moreover, it belongs to the urea cycle.
  • However, it is a situation in which the body’s process of removing ammonia is disrupted, and ammonia levels in the body rise.


Here are the risk factors associated with Arginase deficiency:

  • Hypoglycemia: Generally known as low blood sugar level of the body. The increased content of ammonia in the blood can decrease blood glucose.
  • UTI: Urinary tract infection is usually the result of a high concentration of ammonia in the urine. UTI in women is more common than in men.
  • Hepatic encephalopathy: it happens when your liver is damaged to process the ammonia, and blood carrying ammonia reaches your brain. However, the intoxicated blood damages your nervous tissue and brains cell leading to a coma.
  • Kidney and liver failure: the excess ammonia contaminated reaches the kidney and liver for the functioning of the body.
  • However, excess ammonia content in the body can be hazardous to these organs and lead to permanent damage.
  • Excessive sleepiness and hand tremor are other risk factors associated with arginase deficiency.


Conditions
Inherit metabolism disorder,The rise of ammonia in blood,Genetic mutations
Drugs
Low protien diet,Phenobarbital or carbamazepine
Symptoms
Feeding problems,Seizures,Poor growth,Vomiting,Stiff muscles with increased reflexes (spasticity)

Is there a cure/medications for arginase deficiency?

Arginase deficiency is an inherited metabolic disorder that leads the body to be unable to digest building blocks of protein.

  • It causes amino acids arginine and amino acid to accumulate in the blood flow. The presence of arginine leads to serious problems such as kidney and liver failure.
  • Patients with arginase deficiency are recommended to intake a minimum protein and high calories diet.


Moreover, other cures and treatments of arginase deficiency are as follows:

  • Low protein content food: Since it is a genetic metabolic disorder that reduces the individual capacity for indigestion of protein. Therefore, a low protein content diet is recommended for such patients.
  • Intravenous therapy: since the body can’t break building blocks of protein, so this therapy provides a way to give fluids, medicine, nutrition, or blood directly into the bloodstream through a vein.
  • A Keto diet and antiepileptic drugs are recommended for patients suffering from Arginase deficiency.
  • Hemodialysis: Higher content of ammonia sometimes leads to kidney and liver failure; to avoid such a situation, a machine is attached to the patient. The machine filters wastes, salts, and fluid from your blood when your kidneys are no longer healthy enough to do this work adequately.


Conditions
Inherit metabolism disorder,The rise of ammonia in blood,Genetic mutations
Drugs
Low protien diet,Phenobarbital or carbamazepine
Symptoms
Feeding problems,Seizures,Poor growth,Vomiting,Stiff muscles with increased reflexes (spasticity)

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