About argininemia

What is argininemia?

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 argininemia?

Argininemia results from genetic mutation of gene ARG1 that leads to cause a harmful amount of arginine( body build protein) and ammonia to build up in the body. This disease leads to an imbalanced proliferation of ammonia in the body, which results in serious health issues like coma, kidney and liver failure, UTI, and even death.

This disease is more often visible in newborns, and they can reflect symptoms like:

  • Delayed growth: the baby will not grow properly and tend to have weak muscles
  • Spasticity: It is abnormal muscle contraction due to prolonged muscle congregation. Moreover, it is also associated with damage to the brain and nervous system.
  • Poor appetite: the baby will refuse to eat food several times.
  • Longer sleeping and hyperactivity: either the baby will sleep for a longer time or will be hyperactive during the initial months of birth.
  • Vomiting: due to improper digestion of protein present in milk and other food, the baby will find it difficult to digest Land, and thus vomit it out.
  • Small head size: the baby will have a smaller head as compared to the rest of the body.


Conditions
Causes harmful amounts of arginine and ammonia to build up in the body
Drugs
Intravenous (IV) fluids,Protein intake limited
Sodium benzoate,Sodium phenylbutyrate,Carglumic acid,Glycerol phenylbutyrate,Palonosetron,Ondansetron hydrochloride
Symptoms
Lethargy,Dehydration,Hypotonia,Growth is stunted,Microcephaly,Seizures

What are the causes for argininemia?

The genetic mutation in the ARG1 gene results in Argininemia, which leads to cause a harmful amount of arginine ( body build protein ) and ammonia to build up in the body.

  • It is a urea cycle disorder that leads to the overproduction of ammonia and arginine in the blood.
  • Moreover, this disease leads to an imbalanced proliferation of ammonia in the body, which results in serious health issues like coma, kidney and liver failure, UTI, and even death.
  • This disease is inherited and caused due to change of ARG1 that further leads to the following cause:
  • Argininemia is a urea cycle disorder where the deficiency of the arginase enzyme leads to the imbalanced production of ammonia and arginine (type of amino acid) in the blood.
  • The AGR1 gene is mutated, thus resulting in urea cycle disorder. The ARG1 gene gives directions to make an enzyme called arginase; this catalyst controls the last strides of the urea cycle, which produces urea by extricating nitrogen from arginine.
  • Patients with arginase inadequacy results in missing arginase, and arginine aren't separated as expected.
  • Subsequently, urea can't be produced, and an abundance of nitrogen collects in the blood as ammonia.
  • If the child carries an affected gene from both parents, he will end up having argininemia.


Conditions
Causes harmful amounts of arginine and ammonia to build up in the body
Drugs
Intravenous (IV) fluids,Protein intake limited
Sodium benzoate,Sodium phenylbutyrate,Carglumic acid,Glycerol phenylbutyrate,Palonosetron,Ondansetron hydrochloride
Symptoms
Lethargy,Dehydration,Hypotonia,Growth is stunted,Microcephaly,Seizures

What are the treatments for argininemia?

Argininemia is caused by genetic mutation of the AGR1 gene and results in urea cycle disorder that leads to the overproduction of ammonia and arginine in the blood. Moreover, this disease leads to an imbalanced proliferation of ammonia and arginine in the body which results in serious health issues like coma, kidney and liver failure, UTI, and even death. However, the treatments of argininemia are dietary and some other drugs can support this treatment:

The treatments for Argininemia are as follows:

  • Limited protein intake: in such conditions, the body can’t digest protein-rich foods and supplements. However, the unbroken protein elements reach the blood and result in an overproduction of toxins in the blood.
  • Sodium benzoate: argininemia results in a lack of appetite that can be fixed by using drugs rich in sodium benzoate.
  • Sodium phenylbutyrate: this salt is used with a proper diet to cure inherited disorders of the urea cycle. Moreover, it helps in removing ammonia from the body.
  • Carglumic acid: this drug is also used to remove excess ammonia from the blood. This medicine is prescribed with the diet to prevent and treat hyperammonemia.
  • Glycerol Phenylbutyrate: this is a drug used for patients having urea cycle disorder caused due to an inherited genetic disorder.


Conditions
Causes harmful amounts of arginine and ammonia to build up in the body
Drugs
Intravenous (IV) fluids,Protein intake limited
Sodium benzoate,Sodium phenylbutyrate,Carglumic acid,Glycerol phenylbutyrate,Palonosetron,Ondansetron hydrochloride
Symptoms
Lethargy,Dehydration,Hypotonia,Growth is stunted,Microcephaly,Seizures

What are the risk factors for argininemia?

Argininemia is a urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of ammonia and arginine (type of amino acid) in the blood. It is the result of a genetic mutation of the ARG1 gene.

Here is the list of some other risks associated with this rare inherited genetic mutation.

  • Brain damage: The intoxicated blood rich in ammonia and arginine can damage various parts of the body, including the brain and nervous system. When this blood gets in contact with brain cells and nervous system tissues, it can result in serious problems like disorientation, confusion, coma, and slow reflexes to the stimulus.
  • Liver disease: Hazardous blood can damage tissues of the liver and result in the infective working of the organ. Moreover, liver diseases are the most common cause of high ammonia in the blood. However, Your body can’t transfer ammonia to the liver if there’s a lack of blood flow to it.
  • Kidney failure: Our blood has ammonia, but if it exceeds the required quantity, it has a hazardous effect on the body. If the ammonia and arginine-rich blood get in contact with the kidney regularly, it can lead to kidney failure, and the person might need to get hemodialysis.


Conditions
Causes harmful amounts of arginine and ammonia to build up in the body
Drugs
Intravenous (IV) fluids,Protein intake limited
Sodium benzoate,Sodium phenylbutyrate,Carglumic acid,Glycerol phenylbutyrate,Palonosetron,Ondansetron hydrochloride
Symptoms
Lethargy,Dehydration,Hypotonia,Growth is stunted,Microcephaly,Seizures

Is there a cure/medications for argininemia?

Argininemia is an autosomal recessive, metabolic disorder caused by the loss of the activity of the enzyme, arginase.

  • Arginase is the final enzyme of the urea cycle that produces urea.
  • The human body excretes nitrogen in the form of urea.
  • Due to the loss of enzyme activity, arginine level increases and causes a wide range of abnormal manifestations.
  • The disease is rare, with an incidence rate of 1 in a million.
  • Currently, no permanent cure is available.
  • However, Liver transplantation eliminates argininemia, but the transplantation is rarely necessary.


Since the disease is metabolic, management of the manifestations is perpetual for a lifetime.

  • Active surveillance: Plasma ammonia, amino acid profile, and liver function must be assessed at regular intervals. The interval between the tests depends on age and degree of metabolic stability.
  • Restriction of protein intake: Diet should include food with low protein content to reduce nitrogen intake.
  • Oral nitrogen-scavenging drugs: Daily administration of the drugs such as sodium benzoate, phenylbutyrate, and phenylacetate, to have the level of ammonia in check.
  • Antiseizure medications: Anticonvulsant drugs, phenobarbital, or carbamazepine help control seizures. However, valproate-based medications must be strictly prohibited, as it causes hyperammonemia.
  • Medications that bypass liver metabolism should be preferred.
  • In case of rapid progression to liver fibrosis and cirrhosis, liver transplantation must be considered.


Conditions
Causes harmful amounts of arginine and ammonia to build up in the body
Drugs
Intravenous (IV) fluids,Protein intake limited
Sodium benzoate,Sodium phenylbutyrate,Carglumic acid,Glycerol phenylbutyrate,Palonosetron,Ondansetron hydrochloride
Symptoms
Lethargy,Dehydration,Hypotonia,Growth is stunted,Microcephaly,Seizures

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