$Unique_ID{BRK03416} $Pretitle{} $Title{Acidemia, Propionic} $Subject{Acidemia, Propionic Hyperglycinemia with Ketoacidosis and Leukopenia Ketotic Glycinemia PCC Deficiency Propionyl CoA Carboxylase Deficiency Ketotic Hyperglycinemia Acidemias, Methylmalonic} $Volume{} $Log{} Copyright (C) 1988, 1989 National Organization for Rare Disorders, Inc. 500: Acidemia, Propionic ** IMPORTANT ** It is possible the main title of the article (Propionic Acidemia) 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 Hyperglycinemia with Ketoacidosis and Leukopenia Ketotic Glycinemia PCC Deficiency Propionyl CoA Carboxylase Deficiency Information on the following disorders can be found in the Related Disorders section of this report: Ketotic Hyperglycinemia Acidemias, Methylmalonic 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. Propionic Acidemia is a very rare genetic form of Ketotic Hyperglycinemia. The disorder is due to deficiency of the enzyme propionyl CoA carboxylase, one of the enzymes necessary in the process of breaking down amino acids. Symptoms Propionic Acidemia has an unpredictable course. Many of the symptoms commonly occur later in the course of the disorder and may worsen after excessive protein intake, gastrointestinal or upper respiratory tract infections with fever, or constipation. This disorder is characterized by protein intolerance, acidosis and an abnormally elevated concentration of ketone bodies (ketosis) in the blood and body tissues. Another symptom of Propionic Acidemia is diminished muscle tone. A decrease of blood platelets (thrombocytopenia) may also occur. If left untreated, the acidosis and ketosis may cause dehydration, lethargy, and vomiting. This may lead to coma or seizures which may be life threatening. Without treatment, brain damage and/or generalized or shocklike (myoclonic) seizures will occur. Patients with this disorder may also experience slowed development, mental retardation. Liver abnormalities may include fatty infiltration, degeneration, and swollen liver cells (hepatocytes). The blood of persons with Propionic Acidemia contains an increased amount of glycine and a massive amount of propionate. An EEG (electroencephalograms) may be abnormal. Propionic Acidemia patients may also develop symptoms later in infancy. These tend to be milder than those of the adult form. Human mother's milk contains less protein than formulas or cow's milk. Therefore, some researchers suspect that breast feeding may contribute to the late onset in the milder form of this disorder in some cases. Causes Propionic Acidemia is a genetic disorder transmitted through autosomal recessive genes. (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.) Often the parents of patients with this disorder are related (consanguine). Symptoms are caused by a deficiency of the enzyme propionyl CoA carboxylase, which is needed for the metabolism of some of the building blocks of proteins (amino acids) such as leucine, isoleucine, valine, threonine, and methionine. This deficiency results in increased acidity of the blood. The mechanism which causes the increased levels of the amino acid glycine in the blood is not well understood. Affected Population Propionic Acidemia is a rare hereditary disorder affecting males and females in equal numbers. The form of the disorder which begins later in infancy occurs even less frequently than the form which is present at birth. Related Disorders Symptoms of the following disorders can be similar to those of Propionic Acidemia. 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 Acidemias is a form of Ketotic Hyperglycinemia. (For more information on this disorder, choose "Ketotic Hyperglycinemia" as your search term in the Rare Disease Database.) Methylmalonic Acidemias are one type of organic acidemia. All known organic acidemias are inherited as autosomal recessive traits. They are caused by an enzyme defect in the breakdown (metabolism of one amino acid. This results in an abnormally high level of acid in the blood and body tissues which can cause metabolic acidosis. Drowsiness, coma, and seizures are symptoms of metabolic acidosis. Mental retardation is a long-term consequence. The disorders may be caused by either 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 in people affected by Methylmalonic Acidemias. (For more information on this disorder, choose "Methylmalonic Acidemia" as your search term in the Rare Disease Database.) Therapies: Standard Prenatal diagnosis of Propionic Acidemia is possible by testing the fluid taken from the fetal sac (amniocentesis) for activity of the enzyme propionyl coA carboxylase. However, this method is not very accurate. An alternate method of prenatal diagnosis is measuring the levels of abnormal metabolites such as methyl citrate in the fetal sac fluid. Diagnosis of the disorder in suspected patients and/or relatives of patients who may be carriers involves the measurement of propionic acid in blood or urine, or studies of propionyl- CoA carboxylase activity in white cell (leukocyte) or connective tissue cell (fibroblast) extracts. Treatment for Propionic Acidemia requires fluid and electrolyte therapy. Sodium bicarbonate is used to decrease the acidity of blood and body tissues (acidosis). Or this can be accomplished by either peritoneal dialysis or exchange transfusions. However, treatment must begin as soon as possible and monitoring of blood levels is necessary thereafter. Long-term treatment involves maintenance of a diet low in protein through use of special formulas low in the amino acids leucine, isoleucine, valine, threonine, and methionine. On these restricted diets patients can experience good metabolic control with acceptable growth and development if adequate general nutrition is maintained through use of medical foods. In carnitine deficiency syndromes, the transport of fatty acids into mitochondria for oxidation and energy production is impaired. Because large amounts of glucose must be used to meet the organism's metabolic requirements, hypoglycemia often results, and the patient becomes completely dependent on glucose. Therapies: Investigational Only one patient with Propionic Acidemia has responded to biotin treatment. A therapeutic trial of this coenzyme of PCC can be performed. In carnitine deficiency syndromes, the transport of fatty acids into mitochondria for oxidation and energy production is impaired. Because large amounts of glucose must be used to meet the organism's metabolic requirements, hypoglycemia often results, and the patient becomes completely dependent on glucose. This disease entry is based upon medical information available through December 1989. 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 this disorder, 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 53 Beam Street Nantwich, Cheshire England CW5 5NF Telephone: 0270629782 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 For more 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 PROPIONIC ACIDEMIA: A CLINICAL UPDATE: Barry Wolf, et al.; Journal of Pediatrics (December 1981: issue 99:6). Pp. 835-846. METABOLIC BASIS OF INHERITED DISEASE, 5th ed.: John B. Stanbury, et al., eds.; McGraw Hill, 1983. Pp. 2063-2064. MENDELIAN INHERITANCE IN MAN, 7th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 1001-1002. This Report in the Rare Disease Database is based upon outlines prepared by medical and dental students (1984-1986) at the Medical College of Virginia for their course in human genetics.