$Unique_ID{BRK03776} $Pretitle{} $Title{Glutaricaciduria II} $Subject{Glutaricaciduria II Ethylmalonic Adipicaciduria GA II Glutaric Acidemia II Glutaric Aciduria II Glutaricacidemia II Glutaricaciduria Type IIA GA IIA Multiple Acyl-CoA Dehydrogenase Deficiency Glutaricaciduria IIB Ethylmalonic Adipicaciduria GA IIB Glutaricaciduria I Medium Chain CoA Dehydrogenase Deficiency MCAD} $Volume{} $Log{} Copyright (C) 1987, 1988, 1990, 1992 National Organization for Rare Disorders, Inc. 378: Glutaricaciduria II ** IMPORTANT ** It is possible the main title of the article (Glutaricaciduria II) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Ethylmalonic Adipicaciduria GA II Glutaric Acidemia II Glutaric Aciduria II Glutaricacidemia II Disorder Subdivisions: Glutaricaciduria Type IIA, also known as GA IIA, Multiple Acyl-CoA Dehydrogenase Deficiency Glutaricaciduria IIB, also known as Ethylmalonic Adipicaciduria, GA IIB Information on the following disease can be found in the Related Disorders section of this report: Glutaricaciduria I Medium Chain CoA Dehydrogenase Deficiency (MCAD) 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. There are two forms of Glutaricaciduria II which occur during different stages of life. They are both forms of organic acidemias which are a group of metabolic disorders characterized by excess acid in the blood and urine. 1) Glutaricaciduria IIA (GA IIA), Neonatal Form of Glutaricaciduria II. This neonatal form of Glutaricaciduria II is a very rare, sex-linked hereditary disorder characterized by large amounts of glutaric and other acids in blood and urine. Some researchers believe the disorder is caused by a defect in the breakdown of acyl-CoA compounds. 2) Glutaricaciduria IIB (GA IIB; Ethylmalonic Adipicaciduria), Adult Form of Glutaricaciduria II. This milder form of the disorder is inherited as an autosomal recessive trait. Acidity of the body tissues (metabolic acidosis), and a low blood sugar level (hypoglycemia) without an elevated level of ketones in body tissues (ketosis), occur during adulthood. Large amounts of glutaric acid in the blood and urine are caused by a deficiency of the enzyme "multiple acyl- CoA dehydrogenase". Symptoms 1) Glutaricaciduria IIA is the neonatal form of the disorder, and is the more serious type. This form is characterized by episodes of vomiting and a severely depressed blood sugar level (hypoglycemia). An increased level of ammonia in the blood (hyperammonemia) also occurs. Glutaric, lactic, butyric, isobutyric, 2-methylbutyric, ethylmalonic, adipic, and isovaleric acids (all organic acids) are produced during metabolism of amino acids. These acids are excreted through the urine in dangerously high amounts in persons with Glutaricaciduria. 2) Glutaricaciduria IIB is the adult form of the disorder. This extremely rare form of Glutaricaciduria has been identified in a few adults whose symptoms were vomiting, severe hypoglycemia, and fatty infiltration of the liver. One sibling of a woman with Glutaricaciduria IIB had only nausea, and a 'stale' odor to her breath; she suffered a hypoglycemic coma. Another sibling of this patient had liver disease including jaundice, liver enlargement (hepatomegaly), and hypoglycemia. Excessive amounts of glutaric and ethylmalonic acid were found in the urine of all 3 relatives. Causes The neonatal form of Glutaricaciduria II GA IIA) is caused by deficiency of an element common to all three acyl CoA dehydrogenase enzymes, so that the disorder may also be called Multiple Acyl CoA Dehydrogenase Deficiency. This deficiency causes an excess of several organic acids, especially glutaric acid, in the urine. This type of Glutaricaciduria is inherited through autosomal recessive genes. The adult form of Glutaricaciduria II (GA IIB) is also caused by deficiencies of acyl-CoA dehydrogenase. However, the mode of inheritance in this form of this disorder is autosomal recessive. The deficiencies cause an excess of glutaric and ethylmalonic acids in the urine. 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 GA IIA affects males only, with onset of symptoms at birth. GA IIB affects males and females equally. Symptoms of this form of the disorder first appear during adult life. The neonatal and the adult form of the disorder combined affect less than 200 persons in the United States. Related Disorders Glutaricaciduria I is a rare hereditary metabolic disorder caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase. The disorder is characterized by decreased muscle tone (hypotonia), vomiting, and acidity of the blood. The patient may have involuntary movements of the trunk and limbs (dystonia or athetosis) and mental retardation may also occur. (For more information on this disorder, choose "Glutaricaciduria I" as your search term in the Rare Disease Database.) Medium Chain CoA Dehydrogenase Deficiency (MCAD) is a very rare metabolic disorder characterized by a deficiency of the enzyme CoA dehydrogenase. This enzyme is needed in the breakdown (metabolism) of fats. Low blood sugar (hypoglycemia), lack of energy (lethargy) and possibly coma, associated with fatty changes in the liver, usually occur. During hypoglycemic periods, tests usually show massive amounts of dicarboxylic acid in the urine. There are many rare disorders caused by enzyme deficiencies. To locate these disorders on the Rare Disease Database, choose "Enzyme Deficiency" as your search term. Therapies: Standard Glutaricaciduria is diagnosed when excessive glutaric acid is found in the urine or by enzyme assay in white blood cells (leukocytes). Detection of the disorder in a fetus may be possible by testing for the enzyme acyl-CoA dehydrogenase. It is imperative to test for this disorder as soon after birth as possible. Peritoneal dialysis or hemodialysis may be necessary. The usefulness of restricting the amino acids lysine, hydroxylysine, and tryptophan (which generate glutaric acid), is not established at the present time. Acute episodes of acidity in blood and body tissues (acidosis) and dehydration are treated with fluids and bicarbonate. Many of the adverse effects or organic acidemias are due to secondary carnitine depletion. Such patients should have plasma carnitine measured and, if deficient, begin a supplement of 100-300 mg/kg/day of oral l-carnitine. Genetic counseling is recommended for families of children with Glutaricaciduria. Therapies: Investigational Clinical trials are underway to study stable isotope technique in glucogenesis and Krebs cycle and patient response to treatment. Interested persons may wish to contact: Dr. W.N. Paul Lee Harbor University of CA, Los Angeles Medical Center Dept. of Pediatrics, Box-16 1000 W. Carson St. Torrance, CA 90509 (213) 533-2503 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 Glutaricaciduria, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Lactic Acidosis Support Group P.O. Box 480282 Denver, CO 80248 (303) 287-4953 National Urea Cycle Disorders Foundation 4559 Vauxhall Rd. Richmond, VA 23234-3556 Saul Brusilow, M.D. 301 Children's Medical and Surgical Center Johns Hopkins Hospital 600 N. Wolfe St. Baltimore, MD 21205 (310) 955-0885 Organic Acidemia Association 522 Lander St. Reno, NV 89512 (703) 322-5542 British Organic Acidemia Association 5 Saxon Rd. Ashford, Middlesex TW15 1QL England Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For more information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1274 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 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. 24-27. MENDELIAN INHERITANCE IN MAN, 6th ed: Victor A. McKusick; Johns Hopkins University Press, 1983. Pp. 703, 735, 1038.