$Unique_ID{BRK03559} $Pretitle{} $Title{Carbamyl Phosphate Synthetase Deficiency} $Subject{Carbamyl Phosphate Synthetase Deficiency CPS Deficiency Urea Cycle Disorders Inborn Errors of Urea Synthesis} $Volume{} $Log{} Copyright (C) 1986, 1987, 1990, 1992 National Organization for Rare Disorders, Inc. 307: Carbamyl Phosphate Synthetase Deficiency ** IMPORTANT ** It is possible the main title of the article (Carbamyl Phosphate Synthetase Deficiency) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms CPS Deficiency Urea Cycle Disorders Inborn Errors of Urea Synthesis General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Carbamyl Phosphate Synthetase (CPS) Deficiency is one of several hereditary urea cycle disorders. These disorders are caused by a deficiency of one of the enzymes needed for the synthesis of ammonia into urea, which is normally excreted in the urine. The deficiencies cause an excess of ammonia in the blood and body tissues. (For more information on the following disorders, choose "Urea Cycle Disorder" as your search term in the Rare Disease Database.) In CPS Deficiency the deficient enzyme is carbamyl phosphate synthetase. If left untreated, CPS deficiency manifests itself by an elevated level of toxic ammonia in the blood (hyperammonemia). Untreated these imbalances may lead to brain damage, coma, and eventually to death. Symptoms CPS Deficiency is characterized in infants by an excess of ammonia in the blood (hyperammonemia) with lethargy, coma and seizures. Differential diagnosis is based on the absence of orotate in the urine. Immediate treatment after diagnosis in newborn babies is imperative. If left untreated, brain damage and coma usually occur, which can lead to death. Causes CPS Deficiency is an autosomal recessive hereditary disorder in which the activity of the enzyme carbamyl phosphate synthetase is deficient. This deficiency causes an accumulation of excess ammonia in blood and body tissues. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal.) Affected Population CPS Deficiency is a very rare disorder affecting less than a thousand people in the United States. Males and females are affected equally. Onset of the symptoms occurs at birth, but may not be noticeable for weeks or months as they progress. Related Disorders Organic Acidemias are characterized by hyperammonemia associated with metabolic acidosis, with an anion gap, and, sometimes ketonuria. These disorders are also of genetic origin and affect the Urea Cycle as a secondary phenomenon. Reye Syndrome is a combination of acute brain disease (encephalopathy), and fatty degeneration of the abdominal organs (viscera), which tends to follow some acute virus infections (such as flu and chickenpox) combined with certain toxins (usually aspirin). (For more information, choose "Reye" as your search term in the Rare Disease Database.) The following Urea Cycle Disorders can also be found in the Rare Disease Database. They are all characterized by deficiencies of enzymes that are needed for different steps in the incorporation of ammonium into urea. The symptoms of all Urea Cycle Disorders result from hyperammonemia, in different degrees of severity. N-Acetyl Glutamate Synthetase (NAGS) Deficiency Ornithine Transcarbamylase (OTC) Deficiency Citrullinemia Arginino Succinic Aciduria Arginase Deficiency Therapies: Standard As soon as a urea cycle disorder is suspected, a number of diagnostic tests should be performed, including measurement of pH to assess the acidity of blood and body tissues, plasma levels of ammonia, amino acids, and bicarbonate. However, before the results of these tests are in, treatment of hyperammonemia should be started to prevent coma and/or brain damage. As soon as CPS Deficiency is diagnosed in a newborn baby, dialysis or exchange transfusion should be started. If hyperammoniac coma is present shortly after birth, a combined treatment needs to be started as soon as possible, which may include hemodialysis. Genetic counseling is imperative for the family of children with CPS Deficiency. Enzyme replacement therapy shows potential promise for treatment of urea cycle disorders including CPS Deficiency. Research on this type of therapy is in a preliminary stage. A regimen consisting of acute hemodialysis followed by a restricted intake of protein, plus sodium benzoate, sodium phenylacetate, and orginine or citrulline is being used on an experimental basis. Two new investigational drugs, sodium (or calcium) benzoate, and sodium (or calcium) phenylacetate, are used to enhance waste nitrogen excretion. Thus they prevent toxic ammonia buildup in the blood. These orphan drugs have been developed by Dr. Saul Brusilow (see Resources section of this entry) who is also developing sodium (or calcium) phenylbutyrate which does not have an offensive smell. The drug benzoate/phenylacetate (Ucephan) was approved in 1988 for use in the prevention and treatment of hyperammonemia in patients with urea cycle enzymopathy (UCE) due to enzyme deficiencies. The drug is manufactured by: Kendall McGaw Laboratories, Inc. P.O. Box 25080 Santa Ana, CA 92799-5080 For information on additional therapies that have been designated as Orphan Drugs in the last few months, please return to the main menu of NORD Services and access the Orphan Drug Database. Therapies: Investigational Clinical trials are underway to study L-Carnitine in amino acid and fat metabolism. Interested persons may wish to contact: Charles R. Roe, M.D. Box 3028 Duke University Medical Center Durham, NC 27710 (919) 684-2036 to see if further patients are needed for this research. This disease entry is based upon medical information available through January 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Carbamyl Phosphate Deficiency, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 National Urea Cycle Disorders Foundation 4559 Vauxhall Rd. Richmond, VA 23234-3556 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Saul Brusilow, M.D., Professor of Pediatrics 301 Children's Medical and Surgical Center Johns Hopkins Hospital 600 N. Wolfe Street Baltimore, MD 21205 (310) 955-0885 The National Kidney Foundation 2 Park Ave. New York, NY 10016 (212) 889-2210 (800) 622-9010 American Kidney Fund 6110 Executive Blvd., Suite 1010 Rockville, MD 20852 (301) 881-3052 (800) 638-8299 (800) 492-8361 (MD) Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References DISORDERS OF THE UREA CYCLE: Saul W. Brusilow; Hospital Practice (October 15, 1985; issue 305). Pp. 65-72. SYMPTOMATIC INBORN ERRORS OF METABOLISM IN THE NEONATE: Saul W. Brusilow and David L. Vallee; In: Current Therapy in Neonatal-Perinatal Medicine. Marcel Decker, 1985. Pp. 207-212.