$Unique_ID{BRK03414} $Pretitle{} $Title{Acidemia, Isovaleric} $Subject{Acidemia, Isovaleric Isovaleric Acidaemia Isovalericacidemia Isovaleric Acid CoA Dehydrogenase Deficiency Isovaleryl CoA Carboxylase Deficiency IVA Acidemias, Methylmalonic Glutaricaciduria II Maple Syrup Urine Disease Non-Ketotic Hyperglycinemia (Glycinemia) Propionic Acidemias} $Volume{} $Log{} Copyright (C) 1988, 1989 National Organization for Rare Disorders, Inc. 504: Acidemia, Isovaleric ** IMPORTANT ** It is possible the main title of the article (Isovaleric Acidemia) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names and disorder subdivisions covered by this article. Synonyms Isovaleric Acidaemia Isovalericacidemia Isovaleric Acid CoA Dehydrogenase Deficiency Isovaleryl CoA Carboxylase Deficiency IVA Information on the following disorders may be found in the Related Disorders section of this report: Acidemias, Methylmalonic Glutaricaciduria II Maple Syrup Urine Disease Non-Ketotic Hyperglycinemia (Glycinemia) Propionic Acidemias 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. Isovaleric Acidemia is a hereditary metabolic disorder. It is characterized by a deficiency of the enzyme isovaleryl CoA dehydrogenase. The disorder occurs in both an acute and a chronic intermittent form. In the acute form of Isovaleric Acidemia, vomiting, refusal to eat, and listlessness usually occur. With treatment and low protein diet, the disorder becomes chronically intermittent, and a nearly normal life is possible. Symptoms Isovaleric Acidemia is a rare metabolic disorder that occurs in an acute and a chronic intermittent form. The disorder may start as early as 2 weeks of age or as late as 1 year. It is characterized by attacks of vomiting, lack of appetite and listlessness. Infants with Isovaleric Acidemia become increasingly listless and they sometimes shake or tremble. They often have a lower than normal body temperature (hypothermia). In most cases a strong odor like that of "sweaty feet" occurs. Intermittent episodes are usually triggered by upper respiratory infections or excessive eating of high protein foods. Severe acidity and the presence of ketone bodies in blood and body tissues (ketoacidosis) usually follows and patients may lapse into a coma. Ketoacidotic episodes tend to occur frequently in early infancy and young childhood, but their frequency usually diminishes as the patient grows older. Children with Isovaleric Acidemia often show a natural aversion to protein foods, even at a young age. Causes Isovaleric Acidemia is a genetic disorder inherited through autosomal recessive genes. Symptoms are the result of a deficiency of the enzyme isovaleric co-enzyme A (CoA) dehydrogenase, which is needed for the breakdown of the amino acid leucine. (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 Isovaleric Acidemia is a rare disorder affecting males and females in equal numbers, usually beginning during infancy. Related Disorders Methylmalonic Acidemias are a group of organic acidemias. All known organic acidemias are inherited as autosomal recessive traits. Each is caused by an enzymatic defect in the metabolism of one amino acid. Without treatment, this may result in an abnormally high level of acid in the blood and body tissues (acidosis). In acute cases, drowsiness, coma, seizures and mental retardation may occur. Methylmalonic Acidemias may be caused either by a deficiency of the enzyme methylmalonyl CoA mutase, methylmalonyl racemase, or of adenosylcobalamin synthetic enzymes. Excretion of methylmalonate (a product of amino acid metabolism) in the urine is abnormally high. (For more information, choose Methylmalonic Acidemia" as your search term in the Rare Disease Database.) Glutaricaciduria II (Glutaric Acidemia II) occurs in two forms during two different stages of life. Both forms are organic acidemias, a group of metabolic disorders characterized by the presence of excess acid in the blood and urine. Glutaricaciduria IIA (Glutaric Acidemia IIA), the neonatal onset form of Glutaricaciduria, is a very rare, sex-linked hereditary disorder. It is 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. Glutaricaciduria IIB (Glutaric Acidemia IIB; Ethylmalonic Adipicaciduria), the milder adult onset form of the disorder, is inherited as an autosomal recessive trait. Symptoms may include acidity of the body tissues (acidosis), and a low blood sugar level (hypoglycemia) without an elevated level of ketones in body tissues (ketosis). Large amounts of glutaric acid in the blood and urine are caused by a deficiency of the enzyme "multiple acyl-CoA dehydrogenase" (For more information on this disorder, choose "Glutaricaciduria II" sd your search term in the Rare Disease Database"). Maple Syrup Urine Disease is a hereditary disorder resulting from abnormal metabolism of the four "branched chain" amino acids (protein building blocks), leucine, isoleucine, valine, and alloisoleucine. Without treatment, spasticity alternating with poor muscle tone, convulsions, and coma characterize the disorder. It derives its name from the odor of the patients' urine and sweat. (For more information on this disorder, choose "Maple Syrup Urine" as your search term in the Rare Disease Database.) Non-Ketotic Hyperglycinemia is a genetic disorder characterized as an inborn error of amino acid metabolism. Large amounts of the amino acid glycine tend to accumulate in body fluids, particularly in the cerebrospinal fluid. After severe illness beginning soon after birth, most patients become severely mentally retarded and may develop seizures. (For more information on this disorder, choose "Non-Ketotic Hyperglycinemia" as your search term in the Rare Disease Database.) Propionic Acidemia is a very rare genetic form of Ketotic Hyperglycinemia. The disorder is characterized by a deficiency of the coenzyme propionyl CoA carboxylase, one of the enzymes necessary in the process of breaking down amino acids. Propionic Acidemia occurs in two forms. One form begins at birth and the other is milder, occurring less frequently, with symptoms starting during later infancy. Without treatment, dehydration, drowsiness, lethargy, vomiting, and in some cases coma may develop. (For more information on thisa disorder, choose "Propionic Acidemia" as your search term in the Rare Disease Database.) Therapies: Standard Isovaleric Acidemia can be diagnosed prenatally by measuring the amounts of isovalerylglycine in amniotic fluid and urine. The disorder is treated by a diet with moderate restriction of the amino acid leucine and supplementation of L-carnitine. Other treatment is symptomatic and supportive. Genetic counseling is recommended for families of children with Isovaleric Acidemia. Administration of glycine at 150-300 mg/day is life-saving and may permit normal growth and development. Therapies: Investigational This disease entry is based upon medical information available through December 1988. 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 Isovaleric Acidemia, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Organic Acidemia Association 522 Lander St. Reno, NV 89512 (702) 322-5542 British Organic Acidemia Association 5 Saxon Rd. Ashford, Middlesex TW15 1QL England National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For genetic information and genetic counseling referrals, please contact: Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 References THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.: John B. Stanbury, et al., eds.; McGraw Hill, 1983. Pp. 457-461. THE RESPONSE TO L-CARNITINE AND GLYCINE THERAPY IN ISOVALERIC ACIDAEMIA: C. de Sousa, et al.; European Journal Pediatr (February 1986: issue 144(5)). Pp. 451-456. STABLE ISOTOPE DILUTION ANALYSIS OF ISOVALERYLGLYCINE IN AMNIOTIC FLUID AND URINE AND ITS APPLICATION FOR THE PRENATAL DIAGNOSIS OF ISOVALERIC ACIDEMIA: D.G. Hine, et al.; Pediatr Res (March 1986: issue 20(3)). Pp. 222-226.