$Unique_ID{BRK04097} $Pretitle{} $Title{PEPCK Deficiency, Mitochondrial} $Subject{PEPCK Deficiency Mitochondrial Phosphoenolpyruvate Carboxykinase Deficiency Mitochondrial Korsakoff's Syndrome Leigh's Disease Pyruvate Carboxylase Deficiency Pyruvate Dehydrogenase Deficiency} $Volume{} $Log{} Copyright (C) 1992 National Organization for Rare Disorders, Inc. 875: PEPCK Deficiency, Mitochondrial ** IMPORTANT ** It is possible that the main title of the article (Mitochondrial PEPCK Deficiency) is not the name you expected. PLease check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial Information on the following diseases can be found in the Related Disorders section of this report: Korsakoff's Syndrome Leigh's Disease Pyruvate Carboxylase Deficiency Pyruvate Dehydrogenase Deficiency 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. Mitochondrial PEPCK Deficiency is an extremely rare disorder of carbohydrate metabolism inherited as an autosomal recessive trait. A deficiency of the enzyme phosphoenolpyruvate carboxykinase, which is a key enzyme in the conversion of proteins and fat to glucose (gluconeogenesis), causes an excess of acid in the circulating blood (acidemia). Characteristics of this disorder are low blood sugar (hypoglycemia), loss of muscle tone, an abnormal enlargement of the liver and failure to gain weight and grow normally. Symptoms Patients with Mitochondrial PEPCK Deficiency have an inherited deficiency in the enzyme phosphoenolpyruvate carboxykinase. This enzyme is key in the process of converting proteins and fat to glucose (gluconeogenesis). Major symptoms of this disorder are: Lactic acidemia - presence of excess acid in the circulating blood. Hypoglycemia - an abnormally low blood sugar (glucose) level. Glucose is essential for the functioning of many organs and systems in the body, especially the central nervous system. Hypotonia - loss of muscle tone. Hepatomegaly - abnormal enlargement of the liver. Failure to thrive - inability to gain appropriate weight and grow normally. One patient with Mitochondrial PEPCK Deficiency was reported to have swelling of the arms and legs (Peripheral edema), a disorder in liver function and fever for no apparent reason. It is not known whether these symptoms are related to the disorder. The course of this disorder can be very rapid. Causes Mitochondrial PEPCK Deficiency is a very rare disorder that is inherited as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, 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 for the same trait 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 not show 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 Mitochondrial PEPCK Deficiency affects males and females in equal numbers. This disorder is extremely rare and very few cases have been reported in the medical literature. Related Disorders Symptoms of the following disorders can be similar to those of Mitochondrial PEPCK Deficiency. Comparisons may be useful for a differential diagnosis: Korsakoff's Syndrome is a deficiency of vitamin B-1 (thiamine) which causes cardiovascular, central and peripheral nervous system disturbances. The disease results from either inadequate dietary intake of B-2 or from impaired absorption or utilization of vitamin B-1. It is common in the orient where excessive milling of rice reduces its thiamine content. (For more information on this disorder, choose "Korsakoff" as your search term in the Rare Disease Database). Leigh's Disease is a rare genetic metabolic disorder characterized by lesions of the brain, spinal chord, optic nerve and in some cases, an enlarged heart. Symptoms during infancy may include low body weight, slow growth, tremors, skin changes and interrupted breathing patterns. Progressive neurological disturbances, mental retardation, slurred speech and loss of motor coordination (ataxia) may occur in cases beginning during or after infancy. Leigh's Disease is thought to be inherited through an autosomal recessive trait. (For more information on this disorder, choose "Leigh" as your search term in the Rare Disease Database). Pyruvate Carboxylase Deficiency is a rare metabolic disorder in which there is a deficiency of the enzyme pyruvate carboxylase. This disorder causes an excess presence of acid in the circulating blood (lactic acidemia), neurologic deterioration, vomiting, irritability, inactivity, loss of muscle tone, abnormal eye movements, and seizures. The course of this disorder is progressive. It is inherited through an autosomal recessive trait. (For more information on this disorder, choose "Pyruvate Carboxylase " as your search term in the Rare Disease Database). Pyruvate Dehydrogenase Deficiency is a rare disorder of carbohydrate metabolism inherited through an autosomal recessive trait. Symptoms are caused by a deficiency of the enzyme pyruvate dehydrogenase resulting in persistent or recurrent metabolic acidosis (acidemia). The disorder is manifested by mental retardation and other neurological symptoms. (For more information on this disorder, choose "Pyruvate Dehydrogenase" as your search term in the Rare Disease Database). Therapies: Standard Diagnosis of PEPCK Deficiency can be made shortly after birth by biochemical analysis of fibroblast cells. Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Treatment of severe lactic acidosis with Dichloroacetate appears to improve certain laboratory tests, but does not result in improvement of symptoms. A study published in the November 26, 1992 New England Journal of Medicine indicated that only twelve percent of the Dichloroacetate-treated patients survived and seventeen percent of the placebo-treated group survived. Scientists do not understand why this appears to reduce arterial-blood lactate concentrations and pH, but fails to alter the disease. Research on inborn errors of metabolism, such as PEPCK Deficiency, is ongoing. Scientists are studying the causes of these disorders and trying to design enzyme replacement therapies that will return a missing enzyme to the body. In PEPCK Deficiency patients are unable to metabolize the enzyme. Scientists are investigating the reasons why the enzyme is not metabolized so they can understand how to correct the metabolic defect. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of birth defects in the future. This disease entry is based upon medical information available through December 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 Mitochondrial PEPCK Deficiency, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Lactic Acidosis Support Group 1620 Marie Ave. Denver, CO 80229 (303) 837-2117 or 287-4953 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 Institute Digestive Diseases Information Clearinghouse P.O. Box NDDIC Bethesda, MD 20892 (301) 468-6344 For Genetic Information and Genetic Counseling Referrals: 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 MENDELIAN INHERITANCE IN MAN, 9th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1990. Pp. 1421. THE METABOLIC BASIS OF INHERITED DISEASE, 6th ed.: Charles R. Schriver, et al.; eds., McGraw Hill, 1989. Pp. 878-9. A CONTROLLED CLINICAL TRIAL OF DICHLOROACETATE FOR TREATMENT OF LACTIC ACIDOSIS IN ADULTS: P.W. Stacpoole, et al.; The New England Journal of Medicine; (November 26, 1992, issue 327 (22)). Pp. 1564-69.