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Argininosuccinic Aciduria (ASA)
Thursday, 05 August 2004
Tuesday, 23 November 2004

What

Argininosuccinic Aciduria (ASA) is a rare, genetic disorder that affects the metabolism of nitrogen. Nitrogen comes from the protein found in our diet or from the breakdown of protein in our body that occurs when we are sick. Nitrogen from these sources is usually in the form of a chemical called ammonia. Ammonia must be removed from the body and for this to happen it must first be converted into another chemical called urea. The body converts ammonia to urea by a process called the urea cycle. The urea produced from this cycle will then be excreted by the kidneys in the urine. People with Argininosuccinic Aciduria (ASA) and other urea cycle disorders cannot convert and excrete ammonia. When this happens, ammonia will build up in the body. This build up of ammonia is harmful because it is toxic to the body; especially the brain.

Who

ASA is a genetically inherited disease that mostly affects children. It is estimated that ASA occurs in about 1 in every 70,000 births in the United States. Exactly how often this disease occurs is not known.

Signs and Symptoms

Signs and symptoms of ASA usually occur soon after birth, often with the first feeding. It is possible, however, for the first signs and symptoms not to appear until childhood or even adulthood. Some of the more common signs and symptoms are: 1. Abnormal drowsiness (lethargy) that may lead to coma 2. Persistent vomiting 3. Heavy or rapid breathing 4. Poor feeding, lack of appetite 5. Enlarged liver 6. Seizures 7. Decreased muscle tone 8. Low body temperature 9. Irritability 10. Loss of coordination 11. Disorientation or confusion

Possible Causes

ASA is a genetic disorder that is caused by a defect in one of the enzymes of the urea cycle. The enzyme is named argininosuccinic acid lyase. The job of this enzyme is to convert a compound called argininosuccinic acid into arginine. If there is a lack of argininosuccinic acid lyase, then argininosuccinic acid (one of the chemicals formed in the urea cycle) cannot be converted to arginine. When this happens the urea cycle cannot continue and there is a build up of all parts of the cycle that come before the formation of argininosuccinic acid (including ammonia). A gene for ASA has been identified and this disease is inherited in an autosomal recessive manner. Every person is born with two copies of a gene, one inherited from each parent. In order to have ASA, a child must inherit two copies of the ASA gene, each with a change (mutation). If a child only has one copy of the gene with a change, then he/she will not be affected, but is called a carrier. If both parents have one copy of the gene with a change (both parents are carriers), then there is a 25% chance that each of their children will have ASA, a 50% chance that the child will be a carrier, and a 25% chance that the child will have no copies with a change.

Diagnosis

When any urea cycle disorder is suspected, blood tests are done to measure the amount of ammonia in the body. Ammonia levels will be very high in ASA. Other blood tests may show abnormalities in blood electrolytes and amino acids. Urine and other tests may be done to look for other urea cycle disorders or other disease that cause high levels of ammonia. The diagnosis of ASA is usually made by checking for ASA activity in liver cells, red blood cells or skin cells. People with ASA will show very little ASA activity.

Treatment

ASA is a chronic disease that must be managed over the person’s lifetime. Long term follow-up with doctors and nutritionists familiar with this disease is very important. Ammonia levels must be closely monitored. The main goal of treatment is to control the level of ammonia and avoid any rapid rise in the level of ammonia associated with a viral or other illness. This strategy involves having a strict diet of small amounts of protein with a high number of calories. Medications can also be used to help the body get rid of the excess ammonia.

Prognosis

If ASA goes untreated, the disease can become very serious and even cause death. Mismanagement of the disease and episodes of high ammonia can also cause brain damage, coma and/or death. However, if the disease is treated from birth and all treatments are followed closely, the child can have a very good prognosis, living an almost asymptomatic life. While there is no cure for this disease, gene therapy is being researched to replace argininosuccinic acid lyase in ASA patients.

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
A great site with detailed information about the disease, treatment options, support groups, and ongoing clinical research.

ASA Kids
Great site for ASA families to communicate with each other about issues related to living with ASA. Also good place to find support with other families suffering from ASA.

CLIMB (Children Living with Inherited Metabolic Diseases)
UK Organization dedicated to fighting metabolic diseases through research, awareness and support. This organization provides advice, information and support on all metabolic diseases to children, young adults, and families.

Google Search for Argininosuccinic Aciduria (ASA)

References and Sources

Emedicine.com: Argininosuccinic Aciduria www.emedicine.com/ped/topic2745.htm MedlinePlus: Argininosuccinic Aciduria www.nlm.nih.gov/medlineplus/ency/article/000372.htm OMIM: Argininosuccinic Aciduria www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=207900 National Organization of Rare Diseases: Argininosuccinic Aciduria www.rarediseases.org/ National Urea Cycle Disorders Foundation: Argininosuccinic Aciduria www.nucdf.org/