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What

Carbamoyl phosphate synthetase one (CPS1) deficiency is a rare, inherited disorder that affects the metabolism of nitrogen. Nitrogen is found mostly in proteins and amino acids that we eat or from the breakdown of proteins in our muscles when we are sick. Nitrogen from these sources is usually in the form of ammonia (a special molecule). Ammonia must be removed and to do so it must first be converted to another molecule called urea to be excreted. Patients with CPS1 deficiency cannot convert and excrete ammonia. Ammonia will then build up in the bloodstream and can be toxic to organs.

Who

CPS1 deficiency is a genetically inherited disease that affects mostly children but also can affect adults. There are not many cases of CPS1 deficiency reported and the incidence of CPS1 deficiency is estimated to be about 1 in every 75,000 live births in the United States.

Signs and Symptoms

Signs of CPS1 deficiency usually occur soon after birth, usually right after the first feeding, but sometimes symptoms may not be noticeable until days or weeks later. Here is a list of common signs or symptoms: 1. 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. hypothermia 9. irritability 10. loss of coordination 11. disorientation

Possible Causes

CPS1 deficiency is a genetic disorder that affects one of the biochemical processes in the urea cycle, the process by which the body converts ammonia to urea in order to excrete it. In CPS1 deficiency there is a deficiency of an enzyme called carbamoyl phosphate synthetase (CPS). If there is a lack of CPS1, then ammonia cannot enter the urea cycle. Thus the urea cycle cannot begin and there is a build up of the precursors (including ammonia) in the body. The enzyme is missing because the gene that normally produces it is defective. Every person is born with two copies of every gene, one inherited from each parent. In order to have CPS1 deficiency, a child must receive two bad copies of the CPS1 gene (autosomal recessive inheritance). If the child only has one, then he/she will not be affected but is a carrier for CPS1 deficiency (and can pass this gene to his or her children). If both parents have one copy of the bad CPS1 gene (i.e. both parents are carriers), then there is a 25% chance that their child will have CPS1 deficiency, a 50% chance that the child will be a carrier, and a 25% chance that the child will have no bad CPS1 genes.

Diagnosis

When any urea cycle disorder is suspected, blood tests are done to asses the concentration of ammonia in blood along with other blood tests to assess the content of blood. Ammonia levels will be extremely elevated in CPS1 deficiency patients, while urea levels may be slightly low. Other blood tests may show abnormalities in blood electrolytes, amino acids, and molecules. Urine and other tests may be done to rule out other urea cycle disorders or other disease that cause high levels of ammonia. The diagnosis of CPS1 deficiency is usually done by checking for CPS1 activity in liver cells. A biopsy is taken of the liver and analyzed to see if there is a deficiency of CPS1. People with CPS1 deficiency will show very little CPS1 activity.

Treatment

CPS1 deficiency is a chronic disease that must be managed for the patient’s lifetime. Frequent check-ups with doctors and nutritionists are necessary. Ammonia levels must be closely monitored. Often, many doctors are part of the treatment approach with a clear plan made for what to do if there is an acute attack from CPS1 deficiency. The main goal of treatment is to avoid any acute episodes of high levels of ammonia in the body and to treat any symptoms of the disease. This strategy involves having a very strict diet that restricts proteins but is very high in calories. Medications like arginine supplementation and of sodium benzoate and sodium phenylacetate may be used as intermediates for the urea cycle so nitrogen can be processed. In some affected individuals dialysis may be necessary to remove excess ammonia.

Prognosis

If CPS1 deficiency goes untreated, the disease will cause death. Also, frequent episodes of high ammonia can worsen children’s outcome, causing brain damage, coma and/or death. However, if the disease is treated from birth and all restrictions are followed closely, particularly the diet, the child can have a good prognosis, with relatively little damage from the disease. While there is no cure for this disease, gene therapy is being researched to replace CPS1 in CPS1 deficiency 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.

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.

Save Babies Through Screening
A great website with information on CPS1 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.

Google Search for Carbamoyl Phosphate Synthetase One Deficiency

References and Sources

Emedicine.com: CPS1 deficiency www.emedicine.com/PED/topic314.htm MedlinePlus: CPS1 deficiency www.nlm.nih.gov/medlineplus/ency/article/000372.htm OMIM: CPS1 deficiency www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=237300 National Organization of Rare Diseases: CPS1 deficiency www.rarediseasesnetwork.org/ucdc/cps.htm National Urea Cycle Disorders Foundation: CPS1 deficiency www.nucdf.org/