$Unique_ID{BRK03415} $Pretitle{} $Title{Acidemia, Methylmalonic} $Subject{Acidemia, Methylmalonic Methylmalonic Acidurias Ketotic Hyperglycinemia Propionic Acidemia} $Volume{} $Log{} Copyright (C) 1987, 1988, 1990 National Organization for Rare Disorders, Inc. 427: Acidemia, Methylmalonic ** IMPORTANT ** It is possible the main title of the article (Methylmalonic Acidemias 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 Methylmalonic Acidurias Information on the following diseases can be found in the Related Disorders section of this report: Ketotic Hyperglycinemia Propionic Acidemia 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. Methylmalonic Acidemias are one type of organic acidemia. All known organic acidemias are inherited as autosomal recessive traits. They are caused by an enzymatic defect in the metabolism of one amino acid. This results in an abnormally high level of acid in the blood and body tissues and concomitant metabolic acidosis. Acutely, drowsiness, coma, and seizures may occur. Mental retardation is a long-term consequence. The disorders 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. Symptoms The onset of the Methylmalonic Acidemias usually occurs during the first few months of life. Symptoms may include lethargy, failure to thrive, recurrent vomiting, acidosis, dehydration, respiratory distress, diminished muscle tone, developmental retardation, seizures and/or an enlarged liver. Laboratory findings include an abnormally high amount of methylmalonic acid in the blood and urine. Metabolic acidosis also occurs. Elevated levels of ketone bodies such as acetone in the blood (ketonemia) or in the urine (ketonuria) may develop. An elevated level of ammonia in the blood (hyperammonemia) may also be present. Excessive levels of the amino acid glycine in the blood (hyperglycinemia) and in the urine (hyperglycinuria) is found. The concentration of white blood cells, blood platelets and red blood cells may be lower than normal. Low blood sugar (hypoglycemia) may also occur. Causes The Methylmalonic Acidemias are inherited as autosomal recessive traits. (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.) Related Disorders Symptoms of the following disorders are similar to those of Methylmalonic Acidemias. Comparisons may be useful for a differential diagnosis. Ketotic Hyperglycinemia is a group of hereditary protein metabolism disorders. In each case, a defective enzyme prevents the breakdown of certain amino acids and lipids. High levels of the amino acid glycine and ketones accumulate in the blood and urine. Clinically, affected infants have feeding difficulties and developmental, neurological, digestive, and metabolic problems, as well as increased susceptibility to infections. Often, complications can be avoided with early treatment. The disorders are very rare, with only a few individual cases reported. Methylmalonic Acidemia is a form of Ketotic Hyperglycinemia. (For more information on this disorder, choose "Ketotic Hyperglycinemia" as your search term in the Rare Disease Database.) Propionic Acidemia is a very rare genetic form of Ketotic Hyperglycinemia. This disorder is caused by a deficiency of the enzyme propionyl CoA carboxylase, one of the enzymes necessary in the process of breaking down amino acids. (For more information on this disorder, choose "Propionic Acidemia" as your search term in the Rare Disease Database.) Affected Population The Methylmalonic Acidemias occur at a rate of 1 in 50,000 to 1 in 100,000 live births. Therapies: Standard The diet of children with Methylmalonic Acidemias must be carefully controlled. Treatment includes a low-protein diet and avoidance of the amino acids isoleucine, valine, and threonine. To assure a balanced diet, certain medical foods must be fed to affected children. Pharmacologic doses of vitamin B12 are indicated in the B12-responsive variants. Genetic counseling is recommended for the families of children with Methylmalonic Acidemias. Therapies: Investigational This disease entry is based upon medical information available through March 1990. 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 Methylmalonic Acidemias, 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 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: 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 CLINICAL HETEROGENEITY IN COBALAMIN C VARIANT OF COMBINED HOMOCYSTINURIA AND METHYLMALONIC ACIDURIA: G.A. Mitchell, et al.; Journal Pediatr (March 1986: issue 108,3). Pp. 410-415. THE METABOLIC BASIS OF INHERITED DISEASE, 5th ed.: John B. Stanbury, et al., eds.; McGraw-Hill, 1983. Pp. 486-493.