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What

Argininemia is a rare genetic disease caused by a missing or defective enzyme named arginase. This disease is classified as a nutritional or metabolic disorder because it is caused by an inability of the body to break down protein. High levels of ammonia (a product of the break down of protein) affect a person’s level of consciousness and cause other problems with the neurologic system.

Who

: Argininemia is very rare and affects both males and females equally. This disease does not seem to affect any racial group more commonly than others. Even though a child is born with this disease, it usually does not cause any problems until the age of 2 or 3 years. Argininemia is a genetic disease because it is caused by mutations, or changes, in DNA. These mutations are inherited from both the mother and the father and cause their child to have a missing or defective enzyme. The gene defect for argininemia is called a recessive genetic trait and is unknowingly passed down from generation to generation. A recessive trait means that an affected child has a defect in both genes for the enzyme arginase. The effect of the faulty gene causes problems only when both parents pass a defective gene to their child. The parents are called carriers because they each “carry” one defective gene, but do not show any affects of the disease because they also have a normal copy that produces enough enzyme for the body to break down protein. For each pregnancy of two such carriers, there is a 25% chance that a child will be born with the disease and a 50% chance the child will be a carrier for the gene defect. It is important to understand that these diseases are not contagious and that it is no one’s fault that this happened.

Signs and Symptoms

If ammonia builds up, it is like poison in the body. Ammonia mostly affects the nervous system and may cause the child to have a loss of appetite, feel confused, not think clearly, sleep more than usual, or vomit. If the extra ammonia is not removed quickly, the child may have seizures or may go into a coma. High ammonia can affect all of the parts of the nervous system. It can affect the motor system by causing clumsiness and loss of the ability to walk. It can affect speech and language and affected children can eventually lose their ability to talk. If the level of ammonia is not controlled and remains high, it will cause progressive damage to the brain over time.

Possible Causes

Everyone needs protein, found in meats, dairy products, FISH, eggs, nuts and other foods. The body uses protein to build new tissue and to repair damaged tissue. When someone eats food that contains protein, the body uses what it needs by breaking it down into amino acids (the building blocks of protein) and changes the rest into ammonia. amino acids are used by the body to build skin, muscle, blood and other tissues. Ammonia is a waste product that must be removed from the body. The urea cycle takes place in the liver and breaks down ammonia so it can be excreted in the urine. The urea cycle also makes an amino acid named arginine, which is needed to make new protein. People with urea cycle disorders have a "block" in their urea cycle. They are missing an enzyme needed for the urea cycle to break down protein. This causes a build up of ammonia and arginine in the body. This build up of arginine is where this disease gets its name.

Diagnosis

The diagnosis is made when children with affected nervous systems are found to have high levels of ammonia in their blood along with elevated levels of other specific amino acids. Tests of the urine will also show elevated levels of arginine and other related amino acids. The diagnosis can be confirmed by measuring the level of arginase in liver cells. This is done by liver biopsy, a procedure, done with sedation, in which a thin needle is used to take some liver cells.

Treatment

: Because there is no current cure for this disorder the goals of treatment are to control ammonia levels and provide supportive care. There are drugs available that can help the body get rid of the toxic ammonia. Dialysis can also be used to quickly lower ammonia levels in an emergency. The best treatment for this disorder is a high calorie, low protein diet with amino acid supplements. A diet high in calories ensures that the body will have enough fuel so that it does not have to breakdown its own protein for energy or to make new tissue. The amount of protein in the diet is limited because the less protein eaten, the less ammonia for the urea cycle to remove. Examples of low protein foods are fruits, vegetables and starches. Argininemia is a chronic and progressive disorder requiring long term follow-up with a team of doctors familiar with this disease. The challenge in treating this disorder is to provide enough protein to meet body requirements without overloading the body’s ability to break it down. Visits to the metabolic clinic are needed to make adjustments to food and medication. Regular blood work is necessary to monitor changes in blood levels of ammonia and other nutritional indicators.

Prognosis

If treatment is started early, children with this disorder have a very good prognosis, though they need to maintain their diet for life. If the level of ammonia is not controlled there will be progressive damage to the brain.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

National Urea Cycle Disorders Foundation
The mission of this site is to link families, friends and professionals who are dedicated to the identification, treatment and cure of urea cycle disorders.

Yahoo Health Group
This support group is open to anyone interested in making friends, sharing information and support with others affected by argininemia.

Google Search for Argininemia

References and Sources

OMIM; Online Mendelian Inheritance in Man http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?207800 Author unknown (2004) In Behrman RE, Kliegman RM, Jenson HB (eds) Nelson Textbook of Pediatrics, 17th ed. WB Saunders, p.248. Santos SE, Martins E, Cardosa ML, Barbot C, Vilarinho L, Medina M (2001). Liver transplantation in a case of Argininemia. J Inherit Metab Dis. Dec;24(8):885-7. Prasad AN, Breen JC, Ampola MG, Rosman NP (1997). Argininemia: a treatable genetic cause of progressive spastic diplegia simulating cerebral palsy: case reports and literature review. J Child Neurol. Aug;12(5):301-9. Endres W, Schaller R, Shin YS (1984). Diagnosis and treatment of argininaemia. Characteristics of arginase in human erythrocytes and tissues. J Inherit Metab Dis. 7(1):8.