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Madisons Foundation - Moms And Dads In Search Of Needed Support
NAGS Deficiency
N-Acetylglutamate Synthase Deficiency
Monday, 09 August 2004
Last Updated Monday, 09 August 2004
What
N-Acetylglutamate Synthase Deficiency (NAGS deficiency) is a rare, inherited 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 chemical called ammonia. Ammonia must be removed from the body and to do so 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 NAGS deficiency 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
NAGS deficiency is a very rare genetic disorder that affects mostly children. It is estimated that NAGS deficiency 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 NAGS deficiency 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 confusionPossible Causes
NAGS deficiency is caused by a defect in one of the enzymes of the urea cycle. The enzyme is named N-Acetyl glutamate Synthase (NAGS). This enzyme’s role is to convert a compound called acetyl-coenzyme A (CoA) to N-acetyl glutamate (NAG). NAGS is necessary to prime the first step of the urea cycle. If there is a lack of NAGS, ammonia cannot enter the urea cycle and builds up in the body. A gene for NAGS deficiency 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 NAGS deficiency, a child must inherit two copies of the NAGS 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 NAGS deficiency, 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 NAGS deficiency. 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 NAGS deficiency is usually made by checking for NAGS activity in liver cells. A small piece of the liver is analyzed to see if the enzyme is working correctly. NAGS deficiency patients will show very little NAGS activity.Treatment
NAGS deficiency is a chronic disease that must be managed over the patient’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 to 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. Other medications, like arginine supplementation and carbamylglutamate (a molecule that functions like NAG) may be used to help prime the urea cycle so nitrogen can be processed.Prognosis
If NAGS deficiency 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 normally without many symptoms. While there is no cure for this disease, gene therapy is being researched to replace NAGS in those people born with NAGS deficiency.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.
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.
Contact a Family
Great website to contact other families with disabled children who suffer from rare diseases. This organization is a charity that helps families to cope with the burdens of caring for a child with a rare disease.
Save Babies Through Screening
A great website with information on NAGS deficiency and other urea cycle disorders, screening for the disorder as well as support for those affected. There are also links to other helpful websites.