$Unique_ID{BRK03466} $Pretitle{} $Title{Anemia, Pernicious} $Subject{Anemia, Pernicious Addisonian Pernicious Anemia Addison's Anemia Biermer Anemia Primary Anemia Addison-Biermer Anemia Cytogenic Anemia Malignant Anemia Congenital Absence of Intrinsic Factor Juvenile Pernicious Anemia Megaloblastic Anemia Hereditary Spherocytic Hemolytic Anemia Anemias (General) Vitamin B12 Deficiency} $Volume{} $Log{} Copyright (C) 1986, 1990, 1993 National Organization for Rare Disorders, Inc. 79: Anemia, Pernicious ** IMPORTANT ** It is possible that the main title of the article (Pernicious Anemia) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Addisonian Pernicious Anemia Addison's Anemia Biermer Anemia Primary Anemia Addison-Biermer Anemia Cytogenic Anemia Malignant Anemia Congenital Absence of Intrinsic Factor Disorder Subdivisions: Juvenile Pernicious Anemia Information on the following diseases can be found in the Related Disorders section of this report: Megaloblastic Anemia Hereditary Spherocytic Hemolytic Anemia Anemias (General) Vitamin B12 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. Pernicious Anemia is a rare blood disorder characterized by a deficiency of vitamin B12 (a cobalamin) which is essential for the development of red blood cells. Symptoms generally develop due to a failure of the lining of the stomach (gastric mucosa) to secrete a protein (intrinsic factor) that acts in the small intestine to aid in the absorption of vitamin B12 from the diet. In some cases of Pernicious Anemia, other abnormalities in the intestines prevent absorption of this essential vitamin. Symptoms Pernicious Anemia usually progresses very slowly because the liver stores enough vitamin B12 to last 3 to 5 years. The symptoms begin to appear as the reserves of vitamin B12 in the liver are depleted. Sometimes the first symptom can be a burning feeling in the mouth for which no cause can be found. Once the symptoms of Pernicious Anemia appear, they must be treated or the disease could be life-threatening. These symptoms include weakness, fatigue, an upset stomach (dyspnea), an abnormally rapid heartbeat (tachycardia), and/or chest pains (angina). People with this disorder may also have gastrointestinal problems, such as a profound lack of appetite (anorexia), abdominal pain, indigestion, belching, and/or constipation and diarrhea. Weight loss is common. In some cases this disease may cause an abnormally enlarged liver (hepatomegaly) or spleen (splenomegaly), and it can cause problems with the urogenital system. Some people with Pernicious Anemia may also have involvement of the neurological system. The nerves outside the brain are frequently affected (peripheral nervous system). However, nerves in the spinal cord may also be impaired. Neurological symptoms include numbness or tingling in the arms and/or legs (acroparesthesias), loss of the awareness of vibration and position in the arms and/or legs, impaired ability to coordinate movement (ataxia), a positive Babinski sign (the outward motion of the big toe caused by stroking the sole of the foot), and/or hyperactive reflexes. Some people with Pernicious Anemia may be irritable and depressed, or even experience paranoia (known as megaloblastic madness). Causes Pernicious Anemia is a rare disorder that is known to run in families. A genetic predisposition to this disease may be inherited as an autosomal dominant genetic trait. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease. The gene for intrinsic factor has been located on chromosome 11. 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 dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child. The symptoms of Pernicious Anemia develop due to the failure of the lining of the stomach (gastric mucosa) to secrete a protein called intrinsic factor. Other causes may also be involved including surgery on the digestive tract (gastrostomy), or inability of the small intestine to absorb sufficient nutrients from food (malabsorption syndromes). Pernicious Anemia may also be caused by the absence in the small intestine (ileum) of the sites that absorb vitamin B12, the inability to absorb Vitamin B12 due to local intestinal inflammation (regional enteritis) or surgery on the small intestine, chronic inflammation of the stomach (atrophic gastritis), chronic inflammation of the pancreas (pancreatitis), a condition associated with hypothyroidism characterized by abnormal deposits of mucin in the skin (myxedema), congenital malformations of the small intestine (i.e., blind loop syndrome), or fish tapeworm infestation. (For more information, choose "Gastritis" and "Hypothyroidism," as your search terms in the Rare Disease Database.) Affected Population Pernicious Anemia primarily affects adults and rarely occurs before the patient reaches the age of 35. It is most common in the moderate climates of North America and Europe among people of Scandinavian, English, and Irish descent. Pernicious Anemia is extremely rare in people of Oriental ancestry. A juvenile version of Pernicious Anemia affects infants, children, and adolescents. It resembles the adult version in all respects except certain biochemical reactions. Pernicious Anemia also occurs more frequently in people who have multiple myeloma and various immunoglobulin deficiencies. (For more information on these disorders, choose "Multiple Myeloma," and "Immunodeficiency" as your search terms in the Rare Disease Database.) Related Disorders Symptoms of the following disorders can be similar to those of Pernicious Anemia. Comparisons may be useful for a differential diagnosis: Megaloblastic Anemia is a rare blood disorder characterized by the presence of abnormal white blood cells, low white blood cell counts, and abnormally low levels of circulating platelets. The initial symptoms may include diarrhea, vomiting, a profound loss of appetite (anorexia), and weight loss. Other symptoms may include an abnormally enlarged liver and/or spleen, weakness, heart palpitations, breathing problems, and/or irritability. (For more information, choose "Megaloblastic Anemia" as your search term in the Rare Disease Database.) Hereditary Spherocytic Hemolytic Anemia is a rare inherited blood disorder characterized by the presence of sphere-shaped red blood cells. These cells have difficulty circulating through the spleen resulting in the destruction of red blood cells. The symptoms of Hereditary Spherocytic Hemolytic Anemia may be present at birth or not be apparent for years, and in many people the disease may be so mild that it is not diagnosed. Symptoms may include fatigue and a yellow (jaundice) appearance to the skin. Generally the spleen is enlarged resulting in abdominal discomfort. An infection is the most common trigger of an anemic crisis. Trauma or pregnancy may also cause an anemic crisis. The person may experience fever, headache, loss of appetite, vomiting, leg sores, and/or general weakness. (For more information on this disorder, choose "Hereditary Spherocytic Hemolytic Anemia" as your search term in the Rare Disease Database.) Other types of anemias include: Aplastic Anemia; Hereditary Non- Spherocytic Hemolytic Anemia; Warm Antibody Hemolytic Anemia; Cold Antibody Hemolytic Anemia; Acquired Autoimmune Hemolytic Anemia; Pernicious Anemia; Folic Acid Deficiency Anemia; Blackfan-Diamond Anemia; and Fanconi's Anemia. (For information on other types of Anemias, choose "Anemia" as your search term in the Rare Disease Database.) Vitamin B12 Deficiency is characterized by abnormally low levels of circulating B12 caused by a poor diet, or inadequate absorption of this vitamin by the stomach. Unlike Pernicious Anemia, people with Vitamin B12 Deficiency typically have normal levels of intrinsic factor. Most people with the disorder have abnormally low red blood cell counts (anemia). Symptoms may also include an abnormally enlarged spleen or liver, lack of appetite, intermittent constipation and diarrhea, and/or abdominal pain. This deficiency is very rare due to storage of Vitamin B12 in the liver which lasts for 3 to 5 years. When insufficient B12 is in the diet, the liver releases B12 to compensate for the loss. (For more information, choose "Vitamin B12 Deficiency" as your search term in the Rare Disease Database.) Therapies: Standard Pernicious Anemia is diagnosed through a laboratory test (Schilling test) that measures the ability of the small intestine to absorb vitamin B12. The vitamin is labeled with radioactive cobalt and ingested by mouth. X-ray studies can then determine if the body is properly absorbing this vitamin. Pernicious Anemia is treated by injection of vitamin B12 (as crystalline hydroxocobalamin or cyanocobalamin) into the muscle. A physician must closely monitor the amount of vitamin that is given and adjust the dosage when necessary. People with this disorder must continue to receive maintenance doses of vitamin B12 for life. Genetic counseling may be of benefit for people with Pernicious Anemia and their families. Therapies: Investigational This disease entry is based upon medical information available through June 1993. 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 Pernicious Anemia, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 NIH/National Heart, Blood and Lung Institute (NHLBI) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-4236 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, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 844. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 693, 847. THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. Pp. 766, 1156. HEMATOLOGY, 4th Ed,: William J. Williams, et al,; Editors; McGraw-Hill, Inc., 1990. Pp. 459-461. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. P. 135. LONG-TERM NEUROLOGIC CONSEQUENCES OF NUTRITIONAL VITAMIN B12 DEFICIENCY IN INFANTS. S.M. Graham; J Pediatr (Nov 1992; 121(5:1)). Pp. 710-14. PERNICIOUS ANEMIA. EARLY IDENTIFICATION TO PREVENT PERMANENT SEQUELAE. A.B. Karnad; Postgrad Med (Feb 1991; 91(2)). Pp. 231-34. HUMAN GASTRIC INTRINSIC FACTOR: CHARACTERIZATION OF cDNA AND GENOMIC CLONES AND LOCALIZATION TO HUMAN CHROMOSOME 11. J.E. Hewitt; Genomics (Jun 1990; 10(2)). Pp. 432-40.